# # Metagrowth: A database of "evidences" and "hypotheses" for the study of culture conditions of obligate parasitic bacteria # # (c) Hiroyuki Ogata (Last update May 3, 2004) # # # Evidence-Hypothesis Database for Mycobacterium leprae # Entry E0001 Definition [Mycobacterium leprae.] (T=30C) (ET=E); (T=33C) (ET=E) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Multiplication on medium NM6 + DOPA was optimal at a temperature of 30 degree C [1]. Phenolic glycolipid I (PGL-I) synthesis in modified Dubos medium was optimal at 33 degrees C [2]. In the same condition ATP was optimally maintained at or less than 33 degrees C [2]. Hypothesis IN=(T=30C), ET=E; IN=(T=33C), ET=E. Gene Pathway Reference [1] PubMed:367388 Olitzki AL. "Aeration, temperature and presence of glycerol modifying the multiplication of Mycobacterium leprae." Boll Ist Sieroter Milan. 1978 Sep 30;57(4):398-402.; [2] PubMed:3290244 Franzblau SG, Harris EB. "Biophysical optima for metabolism of Mycobacterium leprae." J Clin Microbiol. 1988 Jun;26(6):1124-9. Update 2003/08/19. // Entry E0002 Definition [Mycobacterium leprae.] Dithiothreitol [cpd:C00265] (ET=U); nitrate reductase [EC:1.7.99.4] (ET=U); ferredoxin-nitrite reductase [EC:1.7.7.1] (ET=U); nitrite reductase [NAD(P)H] [EC:1.7.1.4] (ET=U); (O2=2%) (ET=U) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Compared with M. tuberculosis, M. leprae lost most of the genes for detoxification of reactive oxygen and nitrogen species such as nitric oxide (NO) [1]. Truncated hemoglobins (trHb's) may also explain the susceptibility to the toxic oxygen and nitrogen species [2]. It may be interesting to add in the medium antioxidants (like dithiothreitol) and/or enzymes such as nitrate reductase [EC:1.7.99.4], ferredoxin-nitrite reductase [EC:1.7.7.1] and nitrite reductase (NAD(P)H) [EC:1.7.1.4]. Otherwise we may regulate the atmospheric O2 concentration such as for usual microaerphilic organisms (e.g. 0.2 atom). Hypothesis IN=cpd:C00265, Dithiothreitol, ET=U; IN=EC:1.7.99.4, nitrate reductase, ET=U; IN=EC:1.7.7.1, ferredoxin-nitrite reductase, ET=U; IN=EC:1.7.1.4, nitrite reductase [NAD(P)H], ET=U; IN=(O2=2%), ET=U. Gene Pathway Reference [1] PubMed:12489635 Visca P, Fabozzi G, Milani M, Bolognesi M, Ascenzi P. "Nitric oxide and Mycobacterium leprae pathogenicity." IUBMB Life. 2002 Sep;54(3):95-9.; [2] PubMed:12074585 Visca P, Fabozzi G, Petrucca A, Ciaccio C, Coletta M, De Sanctis G, Bolognesi M, Milani M, Ascenzi P. "The truncated hemoglobin from Mycobacterium leprae." Biochem Biophys Res Commun. 2002 Jun 28;294(5):1064-70. Update 2003/08/19. // Entry E0003 Definition [Mycobacterium leprae.] Fatty acid [cpd:C00162] (ET=S); Malonyl-CoA [cpd:C00083] (ET=S) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence The largest functional groups (paralogs) were found to be involved in the metabolism and modification of fatty acids and polyketides [1]. Polyketide synthesis usually require malonyl-CoA. Hypothesis IN=cpd:C00162, Fatty acid, ET=S; IN=cpd:C00083, Malonyl-CoA, ET=S. Gene Pathway Reference [1] PubMed:11826475 Eiglmeier K, Parkhill J, Honore N, Garnier T, Tekaia F, Telenti A, Klatser P, James KD, Thomson NR, Wheeler PR, Churcher C, Harris D, Mungall K, Barrell BG, Cole ST. "The decaying genome of Mycobacterium leprae." Lepr Rev. 2001 Dec;72(4):387-98. Update 2003/08/19. // Entry E0004 Definition [Mycobacterium leprae.] (pH=7.0) (ET=E); (T=30C) (ET=E); egg-yolk (ET=E); Pyruvate [cpd:C00022] (ET=E); Transferrin[Fe(II)]2 [cpd:C03029] (ET=E); Transferrin[Fe(III)]2 [cpd:C03179] (ET=E); Adenosine [cpd:C00212] (ET=ES); 5-Formyltetrahydrofolate [cpd:C03479] (ET=E); Menadione [cpd:C05377] (ET=E); Phosphatidylcholine [cpd:C00157] (ET=E); N-Acetyl-D-glucosamine [cpd:C00140] (ET=E) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence The ATP generation was measured in cells cultured in Kirchner liquid medium (pH 7.0) enriched with egg-yolk, pyruvate, transferrin (globin protein binding to iron and providing the iron to hemoglobin), adenosine at 30 degree C. Adenosine was critical for ATP generation (optimal 50 micrograms/ml). At pH=6.2 or 6.6, or T=37C, there was no ATP generation. Despite the increase of DNA and ATP, there was no increase in the number of M. leprae cells [1]. Morphological growth and DNA increase were observed when cultured in Kirchner liquid medium at pH 7.0, enriched with adenosine, egg-yolk, folinic acid (5-formyltetrahydrofolate), vitamin K3, lecithin (phosphatidylcholine, a sort of glycerolipid), N-acetylglucosamine at T=30C. ATP did not increase [2]. Hypothesis IN=(pH=7.0), ET=E; IN=(T=30C), ET=E; IN=egg-yolk, ET=E; IN=cpd:C00022, Pyruvate, ET=E; IN=cpd:C03029, Transferrin[Fe(II)]2, ET=E; IN=cpd:C03179, Transferrin[Fe(III)]2, ET=E; IN=cpd:C00212, Adenosine, ET=ES; IN=cpd:C03479, 5-Formyltetrahydrofolate, ET=E; IN=cpd:C05377, Menadione, ET=E; IN=cpd:C00157, Phosphatidylcholine, ET=E; IN=cpd:C00140, N-Acetyl-D-glucosamine, ET=E. Gene Pathway Reference [1] PubMed:11480311 Nakamura M, Matsuoka M. "Limited ATP generation in cells of Mycobacterium leprae Thai-53 strain in enriched Kirchner liquid medium containing adenosine." Int J Lepr Other Mycobact Dis. 2001 Mar;69(1):13-20.; [2] PubMed:9785844 Nakamura M, Matsuoka M. "[Morphological features to be considered as the growth of Mycobacterium leprae Thai-53 strain on a silicon coated slide in a cell-free liquid medium]" Nihon Hansenbyo Gakkai Zasshi. 1998 Jul;67(2):287-91. Japanese. Update 2003/08/19. // Entry E0005 Definition [Mycobacterium leprae.] Palmitate [cpd:C00249] (ET=SE) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae can oxidize 14C-palmitate in axenic culture. This oxidative activity correlates with viability of M. leprae from in vivo suspension. M leprae lose the viability quickly after harvest from hosts. 7H12 liquid medium retained <1% of viability for three weeks. Moderately enlarged nude MFP (mouse foot pad) was the best (not very large MFP) for culture [1]. Hypothesis IN=cpd:C00249, Palmitate, ET=SE. Gene Pathway Reference [1] PubMed:11480310 Truman RW, Krahenbuhl JL. "Viable M. leprae as a research reagent." Int J Lepr Other Mycobact Dis. 2001 Mar;69(1):1-12. Update 2003/08/19. // Entry E0006 Definition [Mycobacterium leprae.] Phospholipid [cpd:C00865] (ET=E); Phosphatidylserine [cpd:C02737] (ET=E); dioleoyl phosphatidyl-L-serine (ET=E); peptides derived from Rv1174c (ET=E) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence To resuscitate dormant Mycobacterium tuberculosis, phospholipids (e.g. commercially available phosphatidyl-L-serine, dioleoyl phosphatidyl-L-serine) and peptides derived from Rv1174c is critical [1]. In M. leprae Rv1174c homolog gene has a frameshift. Hypothesis IN=cpd:C00865, Phospholipid, ET=E; IN=cpd:C02737, Phosphatidylserine, ET=E; IN=dioleoyl phosphatidyl-L-serine, ET=E; IN=peptides derived from Rv1174c, ET=E. Gene Pathway Reference [1] PubMed:11394916 Zhang Y, Yang Y, Woods A, Cotter RJ, Sun Z. "Resuscitation of dormant Mycobacterium tuberculosis by phospholipids or specific peptides." Biochem Biophys Res Commun. 2001 Jun 8;284(2):542-7. Update 2003/08/19. // Entry E0007 Definition [Mycobacterium leprae.] L-Methionine [cpd:C00073] (ET=GD); Methionine metabolism [KEGG:mle00271] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae could be auxotrophic for methionine because metC is a pseudogene [1]. Hypothesis IN=cpd:C00073, L-Methionine, ET=GD. Gene Pathway KEGG:mle00271 Methionine metabolism. Reference [1] PubMed:11234002 Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies RM, Devlin K, Duthoy S, Feltwell T, Fraser A, Hamlin N, Holroyd S, Hornsby T, Jagels K, Lacroix C, Maclean J, Moule S, Murphy L, Oliver K, Quail MA, Rajandream MA, Rutherford KM, Rutter S, Seeger K, Simon S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Taylor K, Whitehead S, Woodward JR, Barrell BG. "Massive gene decay in the leprosy bacillus." Nature. 2001 Feb 22;409(6823):1007-11. Update 2003/08/19. // Entry E0008 Definition [Mycobacterium leprae.] Cobinamide [cpd:C05774] (ET=SD); Vitamin B12 [cpd:C05776] (ET=D) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae could be auxotrophic for cobinamide because the bacterium possesses the synthetic genes for vitamin B12 from cobinamide but lacks genes for the precursor synthesis [1]. Hypothesis IN=cpd:C05774, Cobinamide, ET=SD; IN=cpd:C05776, Vitamin B12, ET=D. Gene Pathway Reference [1] PubMed:11234002 Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies RM, Devlin K, Duthoy S, Feltwell T, Fraser A, Hamlin N, Holroyd S, Hornsby T, Jagels K, Lacroix C, Maclean J, Moule S, Murphy L, Oliver K, Quail MA, Rajandream MA, Rutherford KM, Rutter S, Seeger K, Simon S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Taylor K, Whitehead S, Woodward JR, Barrell BG. "Massive gene decay in the leprosy bacillus." Nature. 2001 Feb 22;409(6823):1007-11. Update 2003/08/19. // Entry E0009 Definition [Mycobacterium leprae.] fatty acids degraded by lipases (ET=D) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae has only two lipase genes whereas M. tuberculosis has 22 lip genes [1]. Hypothesis IN=fatty acids degraded by lipases, ET=D. Gene Pathway Reference [1] PubMed:11234002 Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies RM, Devlin K, Duthoy S, Feltwell T, Fraser A, Hamlin N, Holroyd S, Hornsby T, Jagels K, Lacroix C, Maclean J, Moule S, Murphy L, Oliver K, Quail MA, Rajandream MA, Rutherford KM, Rutter S, Seeger K, Simon S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Taylor K, Whitehead S, Woodward JR, Barrell BG. "Massive gene decay in the leprosy bacillus." Nature. 2001 Feb 22;409(6823):1007-11. Update 2003/08/19. // Entry E0010 Definition [Mycobacterium leprae.] phenolic glycolipid I (ET=U) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence No gene has been identified to produce phenolic glycolipid I (PGL-I) from phthiocerol-dimycocerosate (PDIM). PGL-I is an envelope component unique to M. leprae not present in M. tuberculosis [1]. If possible we may add phenolic glycolipid I in the medium. Hypothesis IN=phenolic glycolipid I, ET=U. Gene Pathway Reference [1] PubMed:11234002 Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies RM, Devlin K, Duthoy S, Feltwell T, Fraser A, Hamlin N, Holroyd S, Hornsby T, Jagels K, Lacroix C, Maclean J, Moule S, Murphy L, Oliver K, Quail MA, Rajandream MA, Rutherford KM, Rutter S, Seeger K, Simon S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Taylor K, Whitehead S, Woodward JR, Barrell BG. "Massive gene decay in the leprosy bacillus." Nature. 2001 Feb 22;409(6823):1007-11. Update 2003/08/19. // Entry E0011 Definition [Mycobacterium leprae.] salicylate-derived mycobactin siderophores (ET=D) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae lacks biosynthetic gene for siderophores [1]. The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for its growth [2]. In spite of abundance of iron in nature, trivalent Fe(III) is very insoluble in aerobic environments at natural pH. In response, numerous microorganisms evolved an iron scavenging system by synthesizing and excreting low molecular mass, Fe(III)-specific ligands termed siderophores to sequester Fe(III). Hypothesis IN=salicylate-derived mycobactin siderophores, ET=D. Gene Pathway Reference [1] PubMed:11234002 Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies RM, Devlin K, Duthoy S, Feltwell T, Fraser A, Hamlin N, Holroyd S, Hornsby T, Jagels K, Lacroix C, Maclean J, Moule S, Murphy L, Oliver K, Quail MA, Rajandream MA, Rutherford KM, Rutter S, Seeger K, Simon S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Taylor K, Whitehead S, Woodward JR, Barrell BG. "Massive gene decay in the leprosy bacillus." Nature. 2001 Feb 22;409(6823):1007-11.; [2] PubMed:10655517 De Voss JJ, Rutter K, Schroeder BG, Su H, Zhu Y, Barry CE 3rd. "The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages." Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1252-7. Update 2003/08/19. // Entry E0012 Definition [Mycobacterium leprae.] alpha,alpha-Trehalose [cpd:C01083] (ET=D) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Trehalose (a disaccharide present in the cytoplasm of mycobacteria) biosynthetic pathway is deficient in M. leprae. Hypothesis IN=cpd:C01083, alpha,alpha-Trehalose, ET=D. Gene Pathway Reference [1] PubMed:10658666 De Smet KA, Weston A, Brown IN, Young DB, Robertson BD. "Three pathways for trehalose biosynthesis in mycobacteria." Microbiology. 2000 Jan;146 ( Pt 1):199-208. Update 2003/08/19. // Entry E0013 Definition [Mycobacterium leprae.] D-Glucuronate [cpd:C00191] (ET=U); N-Acetyl-D-glucosamine [cpd:C00140] (ET=U) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Mycobacterium scrofulaceum (showing similar disease as leprosy) can be grown in Ogawa's or Sauton's media enriched with glucuronic acid and N-acetyl-D-glucosamine [1]. Hypothesis IN=cpd:C00191, D-Glucuronate, ET=U; IN=cpd:C00140, N-Acetyl-D-glucosamine, ET=U. Gene Pathway Reference [1] PubMed:9513348 Sakai T, Sidik H, Matsuo E, Hayakawa R, Wakizaka A. "A genomic study on the cultivable and nerve invading Mycobacterium HI-75 after the recovery 3 months of the inoculation to nude mice." Nihon Hansenbyo Gakkai Zasshi. 1997 Nov;66(3):223-6. Update 2003/08/19. // Entry E0014 Definition [Mycobacterium leprae.] Manganese [cpd:C00034] (ET=CN) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Mn-type superoxide dismutase of M. leprae is playing a defensive role against toxic-free radicals like NO [1]. Hypothesis IN=cpd:C00034, Manganese, ET=CN. Gene Pathway Reference [1] PubMed:9121327 Khare S, Bhutani LK, Rao DN. "Release of reactive nitrogen intermediates from the peripheral blood-derived monocytes/macrophages of leprosy patients stimulated in vitro by tuftsin." Lepr Rev. 1997 Mar;68(1):16-24. Update 2003/08/19. // Entry E0015 Definition [Mycobacterium leprae.] Glycerol [cpd:C00116] (ET=E); Dextran [cpd:C00372] (ET=E); (pH=7.0) (ET=E); fetal calf serum (ET=E) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Glycerin (2%) and dextran (1%) (dextran of MW 200-300 kDa rather than 100-200 kDa) prolonged the ATP production in phosphate buffer (pH 7.0) containing fetal calf serum (10%). Hypothesis IN=cpd:C00116, Glycerol, ET=E; IN=cpd:C00372, Dextran, ET=E; IN=(pH=7.0), ET=E; IN=fetal calf serum, ET=E. Gene Pathway Reference [1] PubMed:8810561 Nakamura M. "[Effects of glycerin and dextran on maintenance of the activity of Mycobacterium leprae in a cell-free liquid medium]" Nippon Rai Gakkai Zasshi. 1996 Jul;65(2):94-9. Japanese. Update 2003/08/19. // Entry E0016 Definition [Mycobacterium leprae.] cell-free extracts of M. tuberculosis (ET=U) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence In many cases, M. leprae metabolic pathways lack one or two enzymes which are present M. tuberculosis (a general observation in the KEGG pathway data [1]). Although the functional consequence of these apparent deficiency (if non-functional or complemented by other pathways) is unclear, it may be interesting to add in the medium for M. leprae the cell-free extracts of M. tuberculosis, if possible. Hypothesis IN=cell-free extracts of M. tuberculosis, ET=U. Gene Pathway Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0017 Definition [Mycobacterium leprae.] Polysaccharide [cpd:C00420] (ET=T) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for polysaccharide (TransportDB [1]). Hypothesis IN=cpd:C00420, Polysaccharide, ET=T. Gene ML0114, ML0112. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0018 Definition [Mycobacterium leprae.] L-Glutamine [cpd:C00064] (ET=GT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for glutamine (TransportDB [1]). Hypothesis IN=cpd:C00064, L-Glutamine, ET=GT. Gene ML0303. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0019 Definition [Mycobacterium leprae.] Metal [cpd:C00050] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for metal (TransportDB [1]). Hypothesis IN=cpd:C00050, Metal, ET=NT. Gene ML0336, ML0335, ML0337. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0020 Definition [Mycobacterium leprae.] D-Ribose [cpd:C00121] (ET=T) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for ribose (TransportDB [1]). Hypothesis IN=cpd:C00121, D-Ribose, ET=T. Gene ML0397, ML0398. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0021 Definition [Mycobacterium leprae.] Oligopeptide [cpd:C00098] (ET=T); Peptide [cpd:C00012] (ET=T); Dipeptide [cpd:C00107] (ET=T) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for oligopeptide, peptide and dipeptide (TransportDB [1]). Hypothesis IN=cpd:C00098, Oligopeptide, ET=T; IN=cpd:C00012, Peptide, ET=T; IN=cpd:C00107, Dipeptide, ET=T. Gene ML0489; ML1122, ML1123, ML1124, ML1121; ML1497. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0022 Definition [Mycobacterium leprae.] Sulfate [cpd:C00059] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for sulfate (TransportDB [1]). Hypothesis IN=cpd:C00059, Sulfate, ET=NT. Gene ML0618, ML0616, ML0617, ML0615; ML2279. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0023 Definition [Mycobacterium leprae.] Cobalt [cpd:C00175] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for cobalt (TransportDB [1]). Hypothesis IN=cpd:C00175, Cobalt, ET=NT. Gene ML0848, ML0849. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0024 Definition [Mycobacterium leprae.] Sugar [cpd:C11477] (ET=T) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for sugar (TransportDB [1]). Hypothesis IN=cpd:C11477, Sugar, ET=T. Gene ML1089, ML1087, ML1088, ML1086; ML1424, ML1425, ML1426, ML1427; ML1768, ML1769, ML1770. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0025 Definition [Mycobacterium leprae.] Iron [cpd:C00023] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for iron(III) (TransportDB [1]). Hypothesis IN=cpd:C00023, Iron, ET=NT. Gene ML1726, ML1729. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0026 Definition [Mycobacterium leprae.] RNA [cpd:C00046] (ET=T) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for ribonucleotide (TransportDB [1]). Hypothesis IN=cpd:C00046, RNA, ET=T. Gene ML1892. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0027 Definition [Mycobacterium leprae.] Orthophosphate [cpd:C00009] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for phosphate (TransportDB [1]). Hypothesis IN=cpd:C00009, Orthophosphate, ET=NT. Gene ML2093, ML2094, ML2095; ML2189, ML2192; ML2260. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0028 Definition [Mycobacterium leprae.] H+ [cpd:C00080] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for proton (TransportDB [1]). ATP synthase. Hypothesis IN=cpd:C00080, H+, ET=NT. Gene ML1142, ML1143, ML1144, ML1145, ML1146. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0029 Definition [Mycobacterium leprae.] Cation [cpd:C01373] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for cation (TransportDB [1]). Hypothesis IN=cpd:C01373, Cation, ET=NT. Gene ML0747; ML1987; ML2671. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0030 Definition [Mycobacterium leprae.] Copper [cpd:C00070] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for cupper ion (TransportDB [1]). Hypothesis IN=cpd:C00070, Copper, ET=NT. Gene ML2000. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0031 Definition [Mycobacterium leprae.] Magnesium [cpd:C00305] (ET=NT); Cobalt [cpd:C00175] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for magnesium and cobalt ion (TransportDB [1]). Hypothesis IN=cpd:C00305, Magnesium, ET=NT; IN=cpd:C00175, Cobalt, ET=NT. Gene ML1090. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0032 Definition [Mycobacterium leprae.] L-Asparagine [cpd:C00152] (ET=GT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for asparagine (TransportDB [1]). Hypothesis IN=cpd:C00152, L-Asparagine, ET=GT. Gene ML1304. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0033 Definition [Mycobacterium leprae.] Aromatic amino acid [cpd:C01021] (ET=GT); L-Tryptophan [cpd:C00078] (ET=GT); L-Tyrosine [cpd:C00082] (ET=GT); L-Phenylalanine [cpd:C00079] (ET=GT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for aromatic amino acids (TransportDB [1]). Hypothesis IN=cpd:C01021, Aromatic amino acid, ET=GT; IN=cpd:C00078, L-Tryptophan, ET=GT; IN=cpd:C00082, L-Tyrosine, ET=GT; IN=cpd:C00079, L-Phenylalanine, ET=GT. Gene ML1305. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0034 Definition [Mycobacterium leprae.] L-Arginine [cpd:C00062] (ET=GT); L-Lysine [cpd:C00047] (ET=GT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for cationic amino acids (TransportDB [1]). Hypothesis IN=cpd:C00062, L-Arginine, ET=GT; IN=cpd:C00047, L-Lysine, ET=GT. Gene ML1974. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0036 Definition [Mycobacterium leprae.] Bile salt [cpd:C01558] (ET=T); Sodium [cpd:C01330] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for sodium ion/bile acid (TransportDB [1]). Hypothesis IN=cpd:C01558, Bile salt, ET=T; IN=cpd:C01330, Sodium, ET=NT. Gene ML0029. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0037 Definition [Mycobacterium leprae.] Calcium [cpd:C00076] (ET=NT); H+ [cpd:C00080] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for calcium ion/proton (TransportDB [1]). Hypothesis IN=cpd:C00076, Calcium, ET=NT; IN=cpd:C00080, H+, ET=NT. Gene ML1267. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0038 Definition [Mycobacterium leprae.] Manganese [cpd:C00034] (ET=NT) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Presence of transporters for manganese (TransportDB [1]). Hypothesis IN=cpd:C00034, Manganese, ET=NT. Gene ML1267. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0051 Definition [Mycobacterium leprae.] Polyphosphate [cpd:C00890] (ET=S); alpha-D-Glucose 6-phosphate [cpd:C00668] (ET=S); D-Glucose [cpd:C00031] (ET=S); Glycolysis / Gluconeogenesis [KEGG:mle00010] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence From glucose to glucose-6P, M. leprae has only polyphosphate-glucose phosphotransferase [EC:2.7.1.63] and does not have glucokinase [EC:2.7.1.2] (according to KEGG [1]). EC:2.7.1.63 use inorganic poly(P) or ATP as phosphate donor, and poly(P) is more efficient than ATP [1]. Long poly(P) is even more efficient than short poly(P). M. leprae lacks the enzymatic step between glucose-1P and glucose-6P [EC:5.4.2.2], which is present in M. tuberculosis (according to KEGG [1]). Although M. leprae has EC:5.4.2.8 that may work in place of EC:5.4.2.2, the bacterium appears not be able to use glycogen and its derivative (e.g. glucose-1P) for the glycolysis. If this is the case, we need to add glucose-6P in addition to poly(P) plus glucose. Hypothesis IN=cpd:C00890, Polyphosphate, ET=S; IN=cpd:C00668, alpha-D-Glucose 6-phosphate, ET=S; IN=cpd:C00031, D-Glucose, ET=S. Gene Pathway KEGG:mle00010 Glycolysis / Gluconeogenesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6.; [2] PubMed:8703950 Hsieh PC, Kowalczyk TH, Phillips NF. "Kinetic mechanisms of polyphosphate glucokinase from Mycobacterium tuberculosis." Biochemistry. 1996 Jul 30;35(30):9772-81. Update 2003/08/19. // Entry E0052 Definition [Mycobacterium leprae.] Acetyl-CoA [cpd:C00024] (ET=D); Glycolysis / Gluconeogenesis [KEGG:mle00010] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Dihydrolipoamide acetyltransferase [EC:2.3.1.12] in the pathway from pyruvate to acetyl-CoA is a pseudogene in M. leprae (according to KEGG [1]). M. leprae also lacks acetyl-CoA ligase [EC:6.2.1.1], which is present in M. tuberculosis and used to generate acetyl-CoA from acetate (according to KEGG [1]). Thus we may add acetyl-CoA. Hypothesis IN=cpd:C00024, Acetyl-CoA, ET=D. Gene Pathway KEGG:mle00010 Glycolysis / Gluconeogenesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0053 Definition [Mycobacterium leprae.] Glyoxylate [cpd:C00048] (ET=U); Glycolate [cpd:C00160] (ET=U); Malate [cpd:C00711] (ET=U); L-Glutamate [cpd:C00025] (ET=U); L-Aspartate [cpd:C00049] (ET=U); Citrate cycle (TCA cycle) [KEGG:mle00020]; Pyruvate metabolism [KEGG:mle00620]; Glyoxylate and dicarboxylate metabolism [KEGG:mle00630] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae does not have [EC:6.4.1.1] (from pyruvate to oxaloacetate). Thus in order for TCA cycle to function, one of the compounds in TCA cycle has to be supplied. M. leprae seems to have several alternative pathways. One such pathway is from phosphoenolpyruvate (PEP) to provide oxaloacetate using [EC:4.1.1.32] (which usually work in the reverse direction) or [EC:4.1.1.31] in the pyruvate metabolic pathway. The pathways from amino acids like glutamate and aspartate generate succinate (by EC:4.1.1.19, EC:2.6.1.19, EC:1.2.1.16) or oxaloacetate (by EC:1.4.3.16), respectively. Another pathway is the use of [EC:2.3.3.9] to generate malate from acetyl-CoA and glyoxylate (in the glyoxylate cycle), but we may have to add glyoxylate in the medium. Glyoxylate may be synthesized from glycolate. In case those pathways are not enough effective, we may directory add in the media malate (mitochondria can uptake malate from cytosol). M. leprae lacks citrate lyase [EC:4.1.3.6] to have oxaloacetate from citrate. Although, this enzyme function when citrate is a sole carbon sources in some organisms, M. leprae appear not able to grow in this style and needs more than citrate. (Other comment on the TCA cycle: M. leprae lacks a step from succinyl-CoA to 2-oxoglutarate [EC:1.2.7.3] which is present in M. tuberculosis. Usually EC:1.2.7.3 is used in reductive Krebs cycle for CO2 fixation. Thus the presence EC:1.2.7.3 in M. tuberculosis is rather strange.) (According to KEGG [1]). Hypothesis IN=cpd:C00048, Glyoxylate, ET=U; IN=cpd:C00160, Glycolate, ET=U; IN=cpd:C00711, Malate, ET=U; IN=cpd:C00025, L-Glutamate, ET=U; IN=cpd:C00049, L-Aspartate, ET=U. Gene Pathway KEGG:mle00020 Citrate cycle (TCA cycle); KEGG:mle00620 Pyruvate metabolism; KEGG:mle00630 Glyoxylate and dicarboxylate metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0054 Definition [Mycobacterium leprae.] D-Glucono-1,5-lactone 6-phosphate [cpd:C01236] (ET=SD); Pentose phosphate pathway [KEGG:mle00030] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Pentose phosphate pathway is complete except the first enzyme [EC:1.1.1.49], which is a pseudogene in M. leprae (according to KEGG [1]). We may have to add D-Glucono-1,5-lactone-6P to skip this step. (Pentose phosphate pathway is important for NADPH, which is important for fatty acids biosynthesis, and ribose-5P for nucleoside synthesis.). Hypothesis IN=cpd:C01236, D-Glucono-1,5-lactone 6-phosphate, ET=SD. Gene Pathway KEGG:mle00030 Pentose phosphate pathway. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0055 Definition [Mycobacterium leprae.] D-Fructose 1-phosphate [cpd:C01094] (ET=S); D-Mannose 6-phosphate [cpd:C00275] (ET=S); D-Mannose 1-phosphate [cpd:C00636] (ET=S); GDP-L-fucose [cpd:C00325] (ET=S); Fructose and mannose metabolism [KEGG:mle00051] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Fructose-1P (but not fructose) may be used to enter glycolysis via glyceraldehydes-3P or frucutose-6P. We may want to add fructose-1P. There is a pathway from D-mannose-1P to beta-D-fructose-6P. If we want to add mannose, it may have to be in the form of D-mannose-6P or D-mannose-1P. M. tuberculosis has a pathway from GDP-D-mannose to GDP-L-fucose. This pathway is not present in M. leprae. We may wan to add GDP-L-fucose, assuming that M. leprae also requires this nucleotide sugar. (According to KEGG [1]). Hypothesis IN=cpd:C01094, D-Fructose 1-phosphate, ET=S; IN=cpd:C00275, D-Mannose 6-phosphate, ET=S; IN=cpd:C00636, D-Mannose 1-phosphate, ET=S; IN=cpd:C00325, GDP-L-fucose, ET=S. Gene Pathway KEGG:mle00051 Fructose and mannose metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0056 Definition [Mycobacterium leprae.] UDP-D-galactose [cpd:C00052] (ET=S); Galactose metabolism [KEGG:mle00052]; Nucleotide sugars metabolism [KEGG:mle00520] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae has two enzymes from UDP-galactose (but not from D-galactose) to D-glucose-1P. D-glucose-1P may not be able to enter in the glycolysis because of the lack of EC:5.4.2.2 in this bacterium. Instead D-glucose-1P may be used to synthesize GDP-L-rhamnose and dTDP-L-rhamnose in the nucleotide sugar metabolism. M. leprae may not be able to use sucrose but M. tuberculosis can. (According to KEGG [1]). Hypothesis IN=cpd:C00052, UDP-D-galactose, ET=S. Gene Pathway KEGG:mle00052 Galactose metabolism; KEGG:mle00520 Nucleotide sugars metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0057 Definition [Mycobacterium leprae.] Malonyl-CoA [cpd:C00083] (ET=D); Pyruvate metabolism [KEGG:mle00620]; Fatty acid biosynthesis (path 1) [KEGG:mle00061] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae cannot synthesize malonyl-CoA from acetyl-CoA using [EC:6.4.1.2]. This indicates a deficiency in fatty acid biosynthesis. (According to KEGG [1]). Hypothesis IN=cpd:C00083, Malonyl-CoA, ET=D. Gene Pathway KEGG:mle00620 Pyruvate metabolism; KEGG:mle00061 Fatty acid biosynthesis (path 1). Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0058 Definition [Mycobacterium leprae.] NH3 [cpd:C00014] (ET=S); Nitrogen metabolism [KEGG:mle00910] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae cannot use nitrate or nitrite, but M. tuberculosis can use them as a source of nitrogen. M. leprae probably uses ammonia (according to KEGG [1]). Hypothesis IN=cpd:C00014, NH3, ET=S. Gene Pathway KEGG:mle00910 Nitrogen metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0059 Definition [Mycobacterium leprae.] L-Methionine [cpd:C00073] (ET=U); L-Cysteine [cpd:C00097] (ET=U); Sulfur metabolism [KEGG:mle00920] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae cannot use inorganic sulfur compounds for sulfur source. M. leprae may use amino acids (Met and Cys) as a source of sulfur (according to KEGG [1]). Hypothesis IN=cpd:C00073, L-Methionine, ET=U; IN=cpd:C00097, L-Cysteine, ET=U. Gene Pathway KEGG:mle00920 Sulfur metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0060 Definition [Mycobacterium leprae.] Vitamin K [cpd:C01628] (ET=U); alpha-Tocopherol [cpd:C02477] (ET=U); trans,trans-Farnesyl diphosphate [cpd:C00448] (ET=U); Geranylgeranyl diphosphate [cpd:C00353] (ET=U); Phytoene [cpd:C05413] (ET=U); Sterol biosynthesis [KEGG:mle00100] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence M. leprae has a pathway from the glycolysis to isopentenyl-PP. Required final products after this pathway is not obvious. A comparison with the M. tuberculosis pathways suggests that vitamin K, vitamin E, fanesyl-PP, all-trans-geranylgeranyl diphosphate, phytoene could be important molecules. Vitamin K (which includes menaquinone) functions in electron transfer. Vitamin E stabilizes membrane structures through anti-oxidation property. In mycobacterium all trans-phytoene is known to be present. (According to KEGG [1]). Hypothesis IN=cpd:C01628, Vitamin K, ET=U; IN=cpd:C02477, alpha-Tocopherol, ET=U; IN=cpd:C00448, trans,trans-Farnesyl diphosphate, ET=U; IN=cpd:C00353, Geranylgeranyl diphosphate, ET=U; IN=cpd:C05413, Phytoene, ET=U. Gene Pathway KEGG:mle00100 Sterol biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0062 Definition [Mycobacterium leprae.] Adenine [cpd:C00147] (ET=S); Adenosine [cpd:C00212] (ET=S); Deoxyadenosine [cpd:C00559] (ET=S); Guanine [cpd:C00242] (ET=S); Guanosine [cpd:C00387] (ET=S); Deoxyguanosine [cpd:C00330] (ET=S); Purine metabolism [KEGG:mle00230] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence De novo synthetic pathways for purines appear complete. Starting compounds for the salvage pathways are adenine, adenosine, deoxyadenosine, guanine, guanosine, and deoxyguanosine. (According to KEGG [1]). Hypothesis IN=cpd:C00147, Adenine, ET=S; IN=cpd:C00212, Adenosine, ET=S; IN=cpd:C00559, Deoxyadenosine, ET=S; IN=cpd:C00242, Guanine, ET=S; IN=cpd:C00387, Guanosine, ET=S; IN=cpd:C00330, Deoxyguanosine, ET=S. Gene Pathway KEGG:mle00230 Purine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0063 Definition [Mycobacterium leprae.] Thymidine [cpd:C00214] (ET=S); CMP [cpd:C00055] (ET=S); UMP [cpd:C00105] (ET=S); Pyrimidine metabolism [KEGG:mle00240] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence De novo synthetic pathways for pyrimidines appear complete. Starting compounds for the salvage pathways are not bases but thymidine, CMP and UMP (according to KEGG [1]). Hypothesis IN=cpd:C00214, Thymidine, ET=S; IN=cpd:C00055, CMP, ET=S; IN=cpd:C00105, UMP, ET=S. Gene Pathway KEGG:mle00240 Pyrimidine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0064 Definition [Mycobacterium leprae.] UDPglucuronate [cpd:C00167] (ET=D); Nucleotide sugars metabolism [KEGG:mle00520] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Among nucleotide sugars (which are donors for glycosyltransferases), M. leprae can generate from glucose-1P to UDP-D-glucose, UDP-D-galactose, dTDP-D-glucose, dTDP-D-galactose, GDP-L-rhamnose, dTDP-L-rhamnose. M. tuberculosis can produce in addition UDP-D-glucuronate (according to KEGG [1]). Hypothesis IN=cpd:C00167, UDPglucuronate, ET=D. Gene Pathway KEGG:mle00520 Nucleotide sugars metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0065 Definition [Mycobacterium leprae.] L-Alanine [cpd:C00041] (ET=GU); Alanine and aspartate metabolism [KEGG:mle00252] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence For alanine, biosynthetic pathway is unknown for M. leprae and M. tuberculosis (according to KEGG [1]). Hypothesis IN=cpd:C00041, L-Alanine, ET=GU. Gene Pathway KEGG:mle00252 Alanine and aspartate metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0066 Definition [Mycobacterium leprae.] L-Lysine [cpd:C00047] (ET=GD); meso-2,6-Diaminoheptanedioate [cpd:C00680] (ET=SD); Lysine biosynthesis [KEGG:mle00300] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Biosynthesis of lysine is deficient with the lacks of [EC:1.3.1.26] and [EC:2.6.1.17]. We may add in the medium lysine and probably meso-2,6-diaminopimelate (according to KEGG [1]). Hypothesis IN=cpd:C00047, L-Lysine, ET=GD; IN=cpd:C00680, meso-2,6-Diaminoheptanedioate, ET=SD. Gene Pathway KEGG:mle00300 Lysine biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0067 Definition [Mycobacterium leprae.] phospholipid degraded by phospholipase C (ET=D); Glycerolipid metabolism [KEGG:mle00561] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence There are no genes for phospholipase C [EC:3.1.4.3] (according to KEGG [1]). We may add in the medium phospholipids degradated with phospholipase C. Hypothesis IN=phospholipid degraded by phospholipase C, ET=D. Gene Pathway KEGG:mle00561 Glycerolipid metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0068 Definition [Mycobacterium leprae.] Acetyl-CoA [cpd:C00024] (ET=D); Tryptophan metabolism [KEGG:mle00380] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Lack of glutaryl-CoA dehydrogenase [EC:1.3.99.7] may pose a problem for generating acetyl-CoA (according to KEGG [1]). Hypothesis IN=cpd:C00024, Acetyl-CoA, ET=D. Gene Pathway KEGG:mle00380 Tryptophan metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0069 Definition [Mycobacterium leprae.] L-Tryptophan [cpd:C00078] (ET=GD); L-Phenylalanine [cpd:C00079] (ET=GD); L-Tyrosine [cpd:C00082] (ET=GD); Phenylalanine, tyrosine and tryptophan biosynthesis [KEGG:mle00400] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence The pathways for tryptophan, phenylalanine, tyrosine are rather complete (the same level as M. tuberculosis), but lacking [EC:5.3.1.24] for tryptophan and [EC:5.4.99.5] for phenylalanine and tyrosine (according to KEGG [1]). Hypothesis IN=cpd:C00078, L-Tryptophan, ET=GD; IN=cpd:C00079, L-Phenylalanine, ET=GD; IN=cpd:C00082, L-Tyrosine, ET=GD. Gene Pathway KEGG:mle00400 Phenylalanine, tyrosine and tryptophan biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0070 Definition [Mycobacterium leprae.] Thiamin [cpd:C00378] (ET=VD); Thiamin diphosphate [cpd:C00068] (ET=CD); Thiamine metabolism [KEGG:mle00730] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence No biosynthetic pathway for thiamine (vitamin B1) and thiamine-PP, which is a coenzyme form of the vitamin (according to KEGG [1]). Some bacterial species require thiamine-PP as a growth factor [2]. A metabolism check system (under development, H. Ogata) suggests M. leprae requires thiamin-PP. Hypothesis IN=cpd:C00378, Thiamin, ET=VD; IN=cpd:C00068, Thiamin diphosphate, ET=CD. Gene Pathway KEGG:mle00730 Thiamine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6.; [2] PubMed:6652579 Van Horn KG, Smibert RM. "Albumin requirement of Treponema denticola and Treponema vincentii." Can J Microbiol. 1983 Sep;29(9):1141-8. Update 2003/08/19. // Entry E0071 Definition [Mycobacterium leprae.] Pyridoxamine [cpd:C00534] (ET=VD); Pyridoxal [cpd:C00250] (ET=VD); Pyridoxine [cpd:C00314] (ET=VD); Pyridoxal phosphate [cpd:C00018] (ET=CD); Vitamin B6 metabolism [KEGG:mle00750] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence No biosynthetic pathway for vitamin B6 (including pyridoxamine, pyridoxal, pyridoxine) from succinate semialdehyde (according to KEGG [1]). Enzymes such as L-serine dehydratase [EC:4.3.1.17] use pyridoxal phosphate as a cofactor [1]. Hypothesis IN=cpd:C00534, Pyridoxamine, ET=VD; IN=cpd:C00250, Pyridoxal, ET=VD; IN=cpd:C00314, Pyridoxine, ET=VD; IN=cpd:C00018, Pyridoxal phosphate, ET=CD. Gene ML1755. Pathway KEGG:mle00750 Vitamin B6 metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0072 Definition [Mycobacterium leprae.] Pantothenate [cpd:C00864] (ET=D); Pantetheine 4'-phosphate [cpd:C01134] (ET=D); CoA [cpd:C00010] (ET=D); Pantothenate and CoA biosynthesis [KEGG:mle00770] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence There are many enzymes for vitamin B5 (i.e. pantothenate) and coenzyme A (CoA) biosynthesis, but not well connected in the form of a continuous pathway. We may add pantothenate, 4-phosphopantetheine, or CoA (according to KEGG [1]). Hypothesis IN=cpd:C00864, Pantothenate, ET=D; IN=cpd:C01134, Pantetheine 4'-phosphate, ET=D; IN=cpd:C00010, CoA, ET=D. Gene Pathway KEGG:mle00770 Pantothenate and CoA biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0073 Definition [Mycobacterium leprae.] Heme [cpd:C00032] (ET=D); Protoporphyrin [cpd:C02191] (ET=SD); Protoporphyrinogen IX [cpd:C01079] (ET=SD); Cobamide coenzyme [cpd:C00194] (ET=CD); Porphyrin and chlorophyll metabolism [KEGG:mle00860] Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence For the synthesis of protoheme, [EC:1.3.3.3] is missing in M. leprae but present in M. tuberculosis (according to KEGG [1]). We may add in the medium, protoheme, protoporphyrin IX or protoporphyrinogen IX. The biosynthesis of vitamin B12 coenzyme (i.e. cobamamide) is almost absent in M. leprae but present in M. tuberculosis (according to KEGG [1]). We may add vitamin B12. A metabolism check system (under development, H. Ogata) suggests M. leprae requires protoporphyrin and vitamin B12. Hypothesis IN=cpd:C00032, Heme, ET=D; IN=cpd:C02191, Protoporphyrin, ET=SD; IN=cpd:C01079, Protoporphyrinogen IX, ET=SD; IN=cpd:C00194, Cobamide coenzyme, ET=CD. Gene Pathway KEGG:mle00860 Porphyrin and chlorophyll metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0074 Definition [Mycobacterium leprae.] dipyrromethane (ET=C) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Porphobilinogen deaminase (HemC) [EC:4.3.1.8] requires dipyrromethane as a cofactor [1-3]. Hypothesis IN=dipyrromethane, ET=C. Gene ML2421. Pathway Reference [1] PubMed:9766005 McNeill LA, Shoolingin-Jordan PM. "Dipyrromethane cofactor assembly in porphobilinogen deaminase." Biochem Soc Trans. 1998 Aug;26(3):S286. No abstract available. ; [2] PubMed:8687374 Shoolingin-Jordan PM, Warren MJ, Awan SJ. "Discovery that the assembly of the dipyrromethane cofactor of porphobilinogen deaminase holoenzyme proceeds initially by the reaction of preuroporphyrinogen with the apoenzyme." Biochem J. 1996 Jun 1;316 ( Pt 2):373-6. ; [3] PubMed:1522882 Louie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Warren MJ, Woodcock SC, Jordan PM. "Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site." Nature. 1992 Sep 3;359(6390):33-9. Update 2003/08/25. // Entry E0075 Definition [Mycobacterium leprae.] Iron [cpd:C00023] (ET=CN); Iron-sulfur [cpd:C00824] (ET=C) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Superoxide dismutase [EC:1.15.1.1] uses iron as a cofactor [1,2]. Glutamate synthase (NADPH) [EC:1.4.1.13] uses iron-sulfur as a cofactor [3]. Hypothesis IN=cpd:C00023, Iron, ET=CN; IN=cpd:C00824, Iron-sulfur, ET=C. Gene ML0072; ML1925; ML0061, ML0062; Pathway Reference [1] PubMed:2669953 Beyer WF Jr, Reynolds JA, Fridovich I. "Differences between the manganese- and the iron-containing superoxide dismutases of Escherichia coli detected through sedimentation equilibrium, hydrodynamic, and spectroscopic studies." Biochemistry. 1989 May 16;28(10):4403-9. ; [2] PubMed:10419947 Santos R, Bocquet S, Puppo A, Touati D. "Characterization of an atypical superoxide dismutase from Sinorhizobium meliloti." J Bacteriol. 1999 Aug;181(15):4509-16. ; [3] PubMed:10357231 Vanoni MA, Curti B. "Glutamate synthase: a complex iron-sulfur flavoprotein." Cell Mol Life Sci. 1999 Apr;55(4):617-38. Review. Update 2003/08/25. // Entry E0076 Definition [Mycobacterium leprae.] Potassium [cpd:C00238] (ET=CN) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence 2-isopropylmalate synthase (LeuA) [EC:2.3.3.13] utilizes potassium (K+) as a cofactor (according to KEGG [1]). Hypothesis IN=cpd:C00238, Potassium, ET=CN. Gene ML2324. Pathway Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0077 Definition [Mycobacterium leprae.] Zinc [cpd:C00038] (ET=CN) Organism Mycobacterium leprae (TAX:1769 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium). Evidence Porphobilinogen synthase (HemB) [EC:4.2.1.24] requires zinc as a cofactor [1]. Hypothesis IN=cpd:C00038, Zinc, ET=CN. Gene Pathway Reference [1] PubMed:2464127 Echelard Y, Dymetryszyn J, Drolet M, Sasarman A. "Nucleotide sequence of the hemB gene of Escherichia coli K12." Mol Gen Genet. 1988 Nov;214(3):503-8. ; [2] PubMed:9287008 Chauhan S, Titus DE, O'Brian MR. "Metals control activity and expression of the heme biosynthesis enzyme delta-aminolevulinic acid dehydratase in Bradyrhizobium japonicum." J Bacteriol. 1997 Sep;179(17):5516-20. Update 2003/08/25. // # # Metagrowth: Evidence-Hypothesis Database for Treponema pallidum # Entry E0201 Definition [Treponema pallidum.] (O2=3%) (ET=E); Dithiothreitol [cpd:C00265] (ET=E); sodium metabisulfite (ET=E) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence T. pallidum is microaerophilic, which is sensitive but require oxygen (O2). The addition of sodium metabisulfite to a Eagle's minimal essential medium with rabbit serum was found to have an effect similar to that of dithiothreitol in the survival of T. pallidum under 3% O2. Analyses revealed that 50% motility was retained longest at O2 concentrations of 1-5%, whether or not dithiothreitol or sodium metabisulfite were present. Concentrations of O2 of 3-10% were optimal for nucleic acid synthesis. Sodium metabisulfite was less effective than dithiothreitol in stimulating nucleic acid synthesis. During incubation under 3% O2, motility was maintained at > 50% for 15 days. The optimal retention of motility and nucleic acid synthesis under microaerobic conditions in the absence of reducing compounds provides evidence that T. pallidum is a microaerophilic organism [1]. Hypothesis IN=(O2=3%), ET=E; IN=cpd:C00265, Dithiothreitol, ET=E; IN=sodium metabisulfite, ET=E. Gene Pathway Reference [1] PubMed:10328016 Cover WH, Norris SJ, Miller JN. "The microaerophilic nature of Treponema pallidum: enhanced survival and incorporation of tritiated adenine under microaerobic conditions in the presence or absence of reducing compounds." Sex Transm Dis. 1982 Jan-Mar;9(1):1-8. Update 2003/08/19. // Entry E0202 Definition [Treponema pallidum.] D-Glucose [cpd:C00031] (ET=TS); Choline [cpd:C00114] (ET=TS) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Glucose is incorporated only in pentose of nucleic acids, aspartate in proteins, glycerol of phosphatidylcholin and phosphatidylglycerol [1,2]. Exogenous choline was incorporated in phosphatidylcholin [2]. Hypothesis IN=cpd:C00031, D-Glucose, ET=TS; IN=cpd:C00114, Choline, ET=TS. Gene Pathway Reference [1] PubMed:9665876 Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Venter JC, et al. "Complete genome sequence of Treponema pallidum, the syphilis spirochete." Science. 1998 Jul 17;281(5375):375-88.; [2] PubMed:7014454 Barbieri JT, Austin FE, Cox CD. "Distribution of glucose incorporated into macromolecular material by treponema pallidum." Infect Immun. 1981 Mar;31(3):1071-7. Update 2003/08/19. // Entry E0203 Definition [Treponema pallidum.] Fatty acid [cpd:C00162] (ET=T) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Treponema pallidum (and Borrelia burgdorferi) incorporates directory fatty acids into the outer membrane [1], because of the lack of lipopolysaccharide in the outer membrane. Gram-negative bacteria exhibit poor permeability of hydrophobic compounds like fatty acids. Hypothesis IN=cpd:C00162, Fatty acid, ET=T. Gene Pathway Reference [1] PubMed:11320119 Cox DL, Radolf JD. "Insertion of fluorescent fatty acid probes into the outer membranes of the pathogenic spirochaetes Treponema pallidum and Borrelia burgdorferi." Microbiology. 2001 May;147(Pt 5):1161-9. Update 2003/08/19. // Entry E0204 Definition [Treponema pallidum.] sn-Glycerol 3-phosphate [cpd:C00093] (ET=TU) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence There is no inorganic phosphate uptake system. Glycerol-3-phosphate through the multiple sugar transporter may be responsible for the source of phosphate [1]. Hypothesis IN=cpd:C00093, sn-Glycerol 3-phosphate, ET=TU. Gene Pathway Reference [1] PubMed:9665876 Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Venter JC, et al. "Complete genome sequence of Treponema pallidum, the syphilis spirochete." Science. 1998 Jul 17;281(5375):375-88. Update 2003/08/19. // Entry E0205 Definition [Treponema pallidum.] Thiamin [cpd:C00378] (ET=R); Thiamin diphosphate [cpd:C00068] (ET=R); albumin (ET=R); Oleate [cpd:C00712] (ET=R) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Treponema denticola and Treponema vincentii require albumin, oleic acid, and thiamine pyrophosphate (TPP) for growth [1]. (Albumin is a generic name for soluble proteins present in the cells and the liquid moiety of animal and plant). Hypothesis IN=cpd:C00378, Thiamin, ET=R; IN=cpd:C00068, Thiamin diphosphate, ET=R; IN=albumin, ET=R; IN=cpd:C00712, Oleate, ET=R. Gene Pathway Reference [1] PubMed:6652579 Van Horn KG, Smibert RM. "Albumin requirement of Treponema denticola and Treponema vincentii." Can J Microbiol. 1983 Sep;29(9):1141-8. Update 2003/08/19. // Entry E0206 Definition [Treponema pallidum.] L-Aspartate [cpd:C00049] (ET=GU); L-Glutamate [cpd:C00025] (ET=GU); L-Histidine [cpd:C00135] (ET=GU); D-Glucose [cpd:C00031] (ET=U); D-Ribose [cpd:C00121] (ET=U) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Predicted chemotaxis specificity includes aspartate, glutamate, histidine, glucose, and ribose [1]. Hypothesis IN=cpd:C00049, L-Aspartate, ET=GU; IN=cpd:C00025, L-Glutamate, ET=GU; IN=cpd:C00135, L-Histidine, ET=GU; IN=cpd:C00031, D-Glucose, ET=U; IN=cpd:C00121, D-Ribose, ET=U. Gene Pathway Reference [1] PubMed:9665876 Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Venter JC, et al. "Complete genome sequence of Treponema pallidum, the syphilis spirochete." Science. 1998 Jul 17;281(5375):375-88. Update 2003/08/19. // Entry E0207 Definition [Treponema pallidum.] Fibronectin [cpd:C00516] (ET=U) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Pathogenic Treponema bind host fibronectin to penetrate organs [1]. Hypothesis IN=cpd:C00516, Fibronectin, ET=U. Gene Pathway Reference [1] PubMed:12833573 Lee JH, Choi HJ, Jung J, Lee MG, Lee JB, Lee KH. "Receptors for Treponema pallidum attachment to the surface and matrix proteins of cultured human dermal microvascular endothelial cells." Yonsei Med J. 2003 Jun 30;44(3):371-8. Update 2003/08/19. // Entry E0208 Definition [Treponema pallidum.] (pH=7.3) (ET=E); ox serum (ET=E); Pyruvate [cpd:C00022] (ET=E); sodium thioglycolate (ET=E); (H2=x%) (ET=E); (CO2=x%) (ET=E); Thioglycolate [cpd:C02086] (ET=E); rabbit serum (ET=E); (T=37C) (ET=E) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence T. pallidum was incubated with and without cells in cell culture medium (pH 7.3), under deoxygenated conditions. Five to ten percent of the treponemes remained motile in cell-treponeme systems of co-incubation. Medium supplemented with ox serum ultrafiltrate, pyruvate, and sodium thioglycolate and gas mixtures containing H2 and CO2 enhanced treponemal survival. Continuous passage of the T. pallidum was not achieved in vitro [1]. A nonpathogenic treponeme were maintained and passaged in thioglycolate medium with 10% heat-inactivated normal rabbit serum at 37 degree C [2]. Hypothesis IN=(pH=7.3), ET=E; IN=ox serum, ET=E; IN=cpd:C00022, Pyruvate, ET=E; IN=sodium thioglycolate, ET=E; IN=(H2=x%), ET=E; IN=(CO2=x%), ET=E; IN=cpd:C02086, Thioglycolate, ET=E; IN=rabbit serum, ET=E; IN=(T=37C), ET=E. Gene Pathway Reference [1] PubMed:789395 Sandok PL, Knight ST, Jenkin HM. "Examination of various cell culture techniques for co-incubation of virulent Treponema pallidum (Nichols I strain) under anaerobic conditions." J Clin Microbiol. 1976 Oct;4(4):360-71.; [2] PubMed:12833573 Lee JH, Choi HJ, Jung J, Lee MG, Lee JB, Lee KH. "Receptors for Treponema pallidum attachment to the surface and matrix proteins of cultured human dermal microvascular endothelial cells." Yonsei Med J. 2003 Jun 30;44(3):371-8. Update 2003/08/19. // Entry E0210 Definition [Treponema pallidum.] Dithiothreitol [cpd:C00265] (ET=E); (O2=3.0%) (ET=E); cobalt chloride (ET=E); Thiamin diphosphate [cpd:C00068] (ET=E); Mannitol [cpd:C00392] (ET=E); L-Histidine [cpd:C00135] (ET=E); catalase [EC:1.11.1.6] (ET=E); superoxide dismutase [EC:1.15.1.1] (ET=E); (O2=5.0-7.0%) (ET=E); Retinol [cpd:C00473] (ET=E); vitamin E acetate (ET=E) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence The effects of the concentrations of dithiothreitol, molecular oxygen, and antioxidants on the in vitro replication of T. pallidum were studied [1]. The optimal dithiothreitol concentration was 0.65-1.62 mM. The optimum oxygen concentration was 3.0%. The optimum concentrations for the water-soluble antioxidants cobalt chloride, cocarboxylase (e.g. thiamin-PP), mannitol, and histidine were 21 nM, 4.3 nM, 0.55 mM, and 0.23 mM, respectively. When combined at these concentrations, the mixture of antioxidants stimulated the in vitro replication. Histidine and mannitol were the most critical. Catalase and superoxide dismutase were investigated for their ability to promote the growth in tissue culture. The optimum concentrations for these enzymes were 10,000 U/liter and 25,000 U/liter, respectively. When these enzymes and the above antioxidants were combined and added to a chemically reduced modified Eagle medium, the treponemes increased an average of 70-fold, compared with an average of 35-fold in cultures lacking them. The medium supported the replication of T. pallidum at oxygen concentrations of 5-7%. The lipid-soluble antioxidants vitamin A and vitamin E acetate were also shown to enhance the in vitro growth in this medium. Hypothesis IN=cpd:C00265, Dithiothreitol, ET=E; IN=(O2=3.0%), ET=E; IN=cobalt chloride, ET=E; IN=cpd:C00068, Thiamin diphosphate, ET=E; IN=cpd:C00392, Mannitol, ET=E; IN=cpd:C00135, L-Histidine, ET=E; IN=EC:1.11.1.6, catalase, ET=E; IN=EC:1.15.1.1, superoxide dismutase, ET=E; IN=(O2=5.0-7.0%), ET=E; IN=cpd:C00473, Retinol, ET=E; IN=vitamin E acetate, ET=E. Gene Pathway Reference [1] PubMed:2285317 Cox DL, Riley B, Chang P, Sayahtaheri S, Tassell S, Hevelone J. "Effects of molecular oxygen, oxidation-reduction potential, and antioxidants upon in vitro replication of Treponema pallidum subsp. pallidum." Appl Environ Microbiol. 1990 Oct;56(10):3063-72. Update 2003/08/19. // Entry E0215 Definition [Treponema pallidum.] Manganese [cpd:C00034] (ET=CNT); Sodium [cpd:C01330] (ET=CN) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for manganese (TransportDB [1]). Oxaloacetate decarboxylase [EC:4.1.1.3] utilizes manganese as well as sodium as cofactors [2]. Hypothesis IN=cpd:C00034, Manganese, ET=CNT; IN=cpd:C01330, Sodium, ET=CN. Gene TP0035, TP0036, TP0034; TP0164, TP0165, TP0166, TP0163; TP0056, TP0057. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:7771770 Jetten MS, Sinskey AJ. "Purification and properties of oxaloacetate decarboxylase from Corynebacterium glutamicum." Antonie Van Leeuwenhoek. 1995;67(2):221-7. Update 2003/08/25. // Entry E0216 Definition [Treponema pallidum.] Sugar [cpd:C11477] (ET=T); D-Ribose [cpd:C00121] (ET=T); D-Galactose [cpd:C00124] (ET=T); (S)-Malate [cpd:C00149] (ET=T); Succinate [cpd:C00042] (ET=T); D-Glucose [cpd:C00031] (ET=T); Glycerol 1-phosphate [cpd:C00623] (ET=T); sn-Glycerol 3-phosphate [cpd:C00093] (ET=T) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for sugar (TransportDB [1]), which include ribose, galactose, malate, succinate, glucose, glycerol-P [2]. Hypothesis IN=cpd:C11477, Sugar, ET=T; IN=cpd:C00121, D-Ribose, ET=T; IN=cpd:C00124, D-Galactose, ET=T; IN=cpd:C00149, (S)-Malate, ET=T; IN=cpd:C00042, Succinate, ET=T; IN=cpd:C00031, D-Glucose, ET=T; IN=cpd:C00623, Glycerol 1-phosphate, ET=T; IN=cpd:C00093, sn-Glycerol 3-phosphate, ET=T. Gene TP0074, TP0075, TP0076; TP0300, TP0301, TP0302; TP0321, TP0322, TP0323; TP0545; TP0804; TP0737. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:9665876 Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Venter JC, et al. "Complete genome sequence of Treponema pallidum, the syphilis spirochete." Science. 1998 Jul 17;281(5375):375-88. Update 2003/08/19. // Entry E0217 Definition [Treponema pallidum.] Molybdenum [cpd:C00150] (ET=NT); Thiamin [cpd:C00378] (ET=T) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for molybdenum (TransportDB [1]). According to [2,3], the transporter is specific to thiamine. Hypothesis IN=cpd:C00150, Molybdenum, ET=NT; IN=cpd:C00378, Thiamin, ET=T. Gene TP0142, TP0143, TP0144. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:9665876 Fraser CM, Norris SJ, Weinstock GM, White O, Sutton GG, Dodson R, Gwinn M, Hickey EK, Clayton R, Ketchum KA, Sodergren E, Hardham JM, McLeod MP, Salzberg S, Peterson J, Khalak H, Richardson D, Howell JK, Chidambaram M, Utterback T, McDonald L, Artiach P, Bowman C, Cotton MD, Venter JC, et al. "Complete genome sequence of Treponema pallidum, the syphilis spirochete." Science. 1998 Jul 17;281(5375):375-88.; [3] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0218 Definition [Treponema pallidum.] Peptide [cpd:C00012] (ET=T) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for peptide (TransportDB [1]). Hypothesis IN=cpd:C00012, Peptide, ET=T. Gene TP0581, TP0582, TP0580, TP0585. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0219 Definition [Treponema pallidum.] Spermidine [cpd:C00315] (ET=T); Putrescine [cpd:C00134] (ET=T) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for spermidine and/or putrescine (TransportDB [1]). Spermidine stabilizes DNA and RNA structure, and enhances translation processes. Spermidine is synthesized from putrescine. There is known transporter in Leishmania for putrescine and spermidine [2]. Hypothesis IN=cpd:C00315, Spermidine, ET=T; IN=cpd:C00134, Putrescine, ET=T. Gene TP0652, TP0653, TP0654, TP0655. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:10924755 Basselin M, Coombs GH, Barrett MP. "Putrescine and spermidine transport in Leishmania." Mol Biochem Parasitol. 2000 Jun;109(1):37-46. Update 2003/08/19. // Entry E0220 Definition [Treponema pallidum.] D-Galactoside [cpd:C02023] (ET=T) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for galactosides (TransportDB [1]). Hypothesis IN=cpd:C02023, D-Galactoside, ET=T. Gene TP0685, TP0686, TP0684. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0221 Definition [Treponema pallidum.] Amino acid [cpd:C00045] (ET=GT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for amino acid (TransportDB [1]). Hypothesis IN=cpd:C00045, Amino acid, ET=GT. Gene TP0120, TP0119; TP0308, TP0309; TP0934. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0222 Definition [Treponema pallidum.] Cobalt [cpd:C00175] (ET=CNT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for cobalt (TransportDB [1]). There is a enzyme [EC:1.1.1.267] requiring cobalt as a cofactor. Hypothesis IN=cpd:C00175, Cobalt, ET=CNT. Gene TP0227; TP0601. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/25. // Entry E0223 Definition [Treponema pallidum.] H+ [cpd:C00080] (ET=NT); Sodium [cpd:C01330] (ET=NT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for H+ or Na+ (TransportDB [1]). Hypothesis IN=cpd:C00080, H+, ET=NT; IN=cpd:C01330, Sodium, ET=NT. Gene TP0424, TP0426, TP0427, TP0428, TP0429, TP0430; TP0527, TP0528, TP0529, TP0530, TP0531, TP0532, TP0533. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0224 Definition [Treponema pallidum.] Copper [cpd:C00070] (ET=NT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for copper (TransportDB [1]). Hypothesis IN=cpd:C00070, Copper, ET=NT. Gene TP1036. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0225 Definition [Treponema pallidum.] L-Alanine [cpd:C00041] (ET=GT); D-Alanine [cpd:C00133] (ET=T); Glycine [cpd:C00037] (ET=GT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for sodium/alanine and alanine (TransportDB [1]). According to KEGG [2], TP0414 is D-alanine and glycine permease (dagA). Hypothesis IN=cpd:C00041, L-Alanine, ET=GT; IN=cpd:C00133, D-Alanine, ET=T; IN=cpd:C00037, Glycine, ET=GT. Gene TP0998, TP0414. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0226 Definition [Treponema pallidum.] Carnitine [cpd:C00487] (ET=TU); Choline [cpd:C00114] (ET=T) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for carnitine/choline (TransportDB [1]). (Carnitine is highly concentrated in animal testes.) Hypothesis IN=cpd:C00487, Carnitine, ET=TU; IN=cpd:C00114, Choline, ET=T. Gene TP0106. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0227 Definition [Treponema pallidum.] Sodium [cpd:C01330] (ET=NT); Calcium [cpd:C00076] (ET=NT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for sodium/calcium (TransportDB [1]). Hypothesis IN=cpd:C01330, Sodium, ET=NT; IN=cpd:C00076, Calcium, ET=NT. Gene TP1034. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0228 Definition [Treponema pallidum.] Chromium [cpd:C06268] (ET=NT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for chromium (TransportDB [1]). Hypothesis IN=cpd:C06268, Chromium, ET=NT. Gene TP0146. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0229 Definition [Treponema pallidum.] L-Glutamate [cpd:C00025] (ET=GT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for glutamate (TransportDB [1]). Hypothesis IN=cpd:C00025, L-Glutamate, ET=GT. Gene TP0555. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0230 Definition [Treponema pallidum.] L-Valine [cpd:C00183] (ET=GT); L-Leucine [cpd:C00123] (ET=GT); L-Isoleucine [cpd:C00407] (ET=GT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for branched-chain amino acid (TransportDB [1]). Hypothesis IN=cpd:C00183, L-Valine, ET=GT; IN=cpd:C00123, L-Leucine, ET=GT; IN=cpd:C00407, L-Isoleucine, ET=GT. Gene TP0265. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0231 Definition [Treponema pallidum.] Sodium [cpd:C01330] (ET=NT); Potassium [cpd:C00238] (ET=NT) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Presence of transporters for sodium/potassium and potassium (TransportDB [1]). Hypothesis IN=cpd:C01330, Sodium, ET=NT; IN=cpd:C00238, Potassium, ET=NT. Gene TP0771; TP0140. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0241 Definition [Treponema pallidum.] Glucose [cpd:C00293] (ET=S); Glycolysis / Gluconeogenesis [KEGG:tpa00010] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Glycolytic pathway is present, in which two steps are catalyzed by unusual pyrophosphate-dependent enzymes (according to KEGG [1]). Hypothesis IN=cpd:C00293, Glucose, ET=S. Gene Pathway KEGG:tpa00010 Glycolysis / Gluconeogenesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0242 Definition [Treponema pallidum.] D-Fructose [cpd:C00095] (ET=S); D-Mannose [cpd:C00159] (ET=S); Fructose and mannose metabolism [KEGG:tpa00051] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Fructose and mannose can enter in the glycolysis (according to KEGG [1]). Hypothesis IN=cpd:C00095, D-Fructose, ET=S; IN=cpd:C00159, D-Mannose, ET=S. Gene Pathway KEGG:tpa00051 Fructose and mannose metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0243 Definition [Treponema pallidum.] Fatty acid [cpd:C00162] (ET=DG); Acetyl-CoA [cpd:C00024] (ET=D) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence A significant deficiency is the absence of fatty acid biosynthesis and degradation (according to KEGG [1]). We may add in the medium fatty acids as well as acetyl-CoA. Hypothesis IN=cpd:C00162, Fatty acid, ET=DG; IN=cpd:C00024, Acetyl-CoA, ET=D. Gene Pathway Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0244 Definition [Treponema pallidum.] Adenine [cpd:C00147] (ET=S); Adenosine [cpd:C00212] (ET=S); Deoxyadenosine [cpd:C00559] (ET=S); Guanine [cpd:C00242] (ET=S); Purine metabolism [KEGG:tpa00230] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence No de novo purine synthetic pathway. Salvage pathway may utilize adenine, adenosine, deoxyadenosine and guanine (according to KEGG [1]). Hypothesis IN=cpd:C00147, Adenine, ET=S; IN=cpd:C00212, Adenosine, ET=S; IN=cpd:C00559, Deoxyadenosine, ET=S; IN=cpd:C00242, Guanine, ET=S. Gene Pathway KEGG:tpa00230 Purine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0245 Definition [Treponema pallidum.] Uracil [cpd:C00106] (ET=S); Cytidine [cpd:C00475] (ET=S); dUMP [cpd:C00365] (ET=S); Pyrimidine metabolism [KEGG:tpa00240] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence No de novo pyrimidine synthetic pathway. Salvage pathway may utilize uracil, cytidine, dUMP (according to KEGG [1]). Hypothesis IN=cpd:C00106, Uracil, ET=S; IN=cpd:C00475, Cytidine, ET=S; IN=cpd:C00365, dUMP, ET=S. Gene Pathway KEGG:tpa00240 Pyrimidine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0246 Definition [Treponema pallidum.] Amino acid [cpd:C00045] (ET=GD); Glutamate metabolism [KEGG:tpa00251]; [KEGG:PATH:tpa00252]; Glycine, serine and threonine metabolism [KEGG:tpa00260]; Methionine metabolism [KEGG:tpa00271]; Cysteine metabolism [KEGG:tpa00272]; Valine, leucine and isoleucine degradation [KEGG:tpa00280]; Lysine biosynthesis [KEGG:tpa00300]; Arginine and proline metabolism [KEGG:tpa00330] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Except for a few interconversion enzymes, there are no biosynthetic pathways for different amino acids (according to KEGG [1]). We have to add all the 20 amino acids. Hypothesis IN=cpd:C00045, Amino acid, ET=GD. Gene Pathway KEGG:tpa00251 Glutamate metabolism; KEGG:PATH:tpa00252 ; KEGG:tpa00260 Glycine, serine and threonine metabolism; KEGG:tpa00271 Methionine metabolism; KEGG:tpa00272 Cysteine metabolism; KEGG:tpa00280 Valine, leucine and isoleucine degradation; KEGG:tpa00300 Lysine biosynthesis; KEGG:tpa00330 Arginine and proline metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0247 Definition [Treponema pallidum.] Thiamin diphosphate [cpd:C00068] (ET=CD); Thiamine metabolism [KEGG:tpa00730] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence No thiamin biosynthetic pathway (according to KEGG [1]). Transketolase A (tktA) [EC:2.2.1.1] uses thiamin diphosphate as a cofactor [2]. Hypothesis IN=cpd:C00068, Thiamin diphosphate, ET=CD. Gene TP0560. Pathway KEGG:tpa00730 Thiamine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6.; [2] PubMed:9767190 Kovina MV, Selivanov VA, Kochevova NV, Kochetov GA. "Kinetic investigation of cooperativity in coenzyme binding by transketolase active sites." Biochemistry (Mosc). 1998 Aug;63(8):988-95. Update 2003/08/19. // Entry E0248 Definition [Treponema pallidum.] Riboflavin [cpd:C00255] (ET=VD); FAD [cpd:C00016] (ET=CD); Riboflavin metabolism [KEGG:tpa00740] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence No synthetic pathway for riboflavin and FAD, although FAD can be generated from riboflavin (according to KEGG [1]). A metabolism check system (under development, H. Ogata) suggests T. pallidum requires FAD and FMN. Hypothesis IN=cpd:C00255, Riboflavin, ET=VD; IN=cpd:C00016, FAD, ET=CD. Gene Pathway KEGG:tpa00740 Riboflavin metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0249 Definition [Treponema pallidum.] Nicotinate [cpd:C00253] (ET=SD); Nicotinamide [cpd:C00153] (ET=SD); Nicotinate and nicotinamide metabolism [KEGG:tpa00760] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence No de novo biosynthesis of nicotinate or nicotinamide, which are precursors of NAD+ and NADP+ (according to KEGG [1]). Hypothesis IN=cpd:C00253, Nicotinate, ET=SD; IN=cpd:C00153, Nicotinamide, ET=SD. Gene Pathway KEGG:tpa00760 Nicotinate and nicotinamide metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0250 Definition [Treponema pallidum.] Pantetheine 4'-phosphate [cpd:C01134] (ET=SD); CoA [cpd:C00010] (ET=SD); Pantothenate and CoA biosynthesis [KEGG:tpa00770] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence No coenzyme A (CoA) biosynthesis (according to KEGG [1]). We may add in the medium a precursor pantetheine 4'-phosphate or CoA. Hypothesis IN=cpd:C01134, Pantetheine 4'-phosphate, ET=SD; IN=cpd:C00010, CoA, ET=SD. Gene Pathway KEGG:tpa00770 Pantothenate and CoA biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0251 Definition [Treponema pallidum.] Biotin [cpd:C00120] (ET=CD); Biotin metabolism [KEGG:tpa00780] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence There is no biotin biosynthetic pathway (according to KEGG [1]) but a metabolism check system (under development, H. Ogata) suggests T. pallidum requires biotin. Hypothesis IN=cpd:C00120, Biotin, ET=CD. Gene Pathway KEGG:tpa00780 Biotin metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0252 Definition [Treponema pallidum.] Folic acid [cpd:C00504] (ET=D); Folate biosynthesis [KEGG:tpa00790] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence There is no folate biosynthetic pathway (according to KEGG [1]). (Folate is a vitamin form of a coenzyme, tetrahydrofolate). Hypothesis IN=cpd:C00504, Folic acid, ET=D. Gene Pathway KEGG:tpa00790 Folate biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0253 Definition [Treponema pallidum.] Iron [cpd:C00023] (ET=CN); Iron-sulfur [cpd:C00824] (ET=C) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Ribonucleoside-diphosphate reductase [EC:1.17.4.1] uses iron and ATP as cofactors [1]. Glutamate synthase (NADPH) [EC:1.4.1.13] uses iron-sulfur as a cofactor [2]. Hypothesis IN=cpd:C00023, Iron, ET=CN; IN=cpd:C00824, Iron-sulfur, ET=C. Gene TP0053; TP1008; TP0735. Pathway Reference [1] PubMed:3544706 Cory JG, Sato A, Brown NC. "Protein properties of the subunits of ribonucleotide reductase and the specificity of the allosteric site(s)." Adv Enzyme Regul. 1986;25:3-19. ; [2] PubMed:10357231 Vanoni MA, Curti B. "Glutamate synthase: a complex iron-sulfur flavoprotein." Cell Mol Life Sci. 1999 Apr;55(4):617-38. Review. Update 2003/08/25. // Entry E0254 Definition [Treponema pallidum.] Magnesium [cpd:C00305] (ET=CN) Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Enolase [EC:4.2.1.11] uses magnesium as a cofactor [1]. Hypothesis IN=cpd:C00305, Magnesium, ET=CN. Gene TP0817. Pathway Reference [1] PubMed:8994873 Reed GH, Poyner RR, Larsen TM, Wedekind JE, Rayment I. "Structural and mechanistic studies of enolase." Curr Opin Struct Biol. 1996 Dec;6(6):736-43. Review. Update 2003/08/25. // Entry E0255 Definition [Treponema pallidum.] Pyridoxal phosphate [cpd:C00018] (ET=C); Pyridoxine [cpd:C00314] (ET=V); D-Glutamine and D-glutamate metabolism [KEGG:tpa00471] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Glutamate racemase (murI) [EC:5.1.1.3] is a pyridoxal-phosphate protein (according to KEGG [1]). Thus pyridoxal-phosphate may be important for Treponema. However, there is also a counter evidence. MurI activity could be independent of the cofactor [2,3]. Hypothesis IN=cpd:C00018, Pyridoxal phosphate, ET=C; IN=cpd:C00314, Pyridoxine, ET=V. Gene TP0406. Pathway KEGG:tpa00471 D-Glutamine and D-glutamate metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6.; [2] PubMed:8385993 Gallo KA, Knowles JR. "Purification, cloning, and cofactor independence of glutamate racemase from Lactobacillus." Biochemistry. 1993 Apr 20;32(15):3981-90. ; [3] PubMed:1358877 Choi SY, Esaki N, Yoshimura T, Soda K. "Reaction mechanism of glutamate racemase, a pyridoxal phosphate-independent amino acid racemase." J Biochem (Tokyo). 1992 Jul;112(1):139-42. Update 2003/08/25. // Entry E0256 Definition [Treponema pallidum.] D-Galactose [cpd:C00124] (ET=S); Fructose and mannose metabolism [KEGG:tpa00051] Organism Treponema pallidum (TAX:160 Bacteria; Spirochaetes; Spirochaetes (class); Spirochaetales; Spirochaetaceae; Treponema). Evidence Galactose may enter in the glycolysis (according to KEGG [1]). Hypothesis IN=cpd:C00124, D-Galactose, ET=S. Gene Pathway KEGG:tpa00051 Fructose and mannose metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // # # Evidence-Hypothesis Database for Rickettsia prowazekii and Rickettsia conorii. # Entry E0401 Definition [Rickettsia prowazekii; Rickettsia conorii.] Pyruvate [cpd:C00022] (ET=DSCR); Glycolysis / Gluconeogenesis [KEGG:rpr00010]; Glycolysis / Gluconeogenesis [KEGG:rco00010] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Glycolysis is absent [1]. So pruvate cannot be synthesized by this pathway. However, pyruvate dehydrogenase E1/E2 and dihydrolipoamide dehydrogenase are present to generate acetyl-CoA using pyruvate as a substrate (according to KEGG [2]). In addition, phosphatidylserine decarboxylase [EC:4.1.1.65] present in Rickettsia is known to use pyruvate as a cofactor [3]. We have to add pyruvate in the medium. It is worth to notice that Mitochondria, whose bacterial closest relatives are Rickettsia, have pyruvate carrier. Hypothesis IN=cpd:C00022, Pyruvate, ET=DSCR. Gene RP241; RC0325. Pathway KEGG:rpr00010 Glycolysis / Gluconeogenesis; KEGG:rco00010 Glycolysis / Gluconeogenesis. Reference [1] PubMed:9823893 Andersson SG, Zomorodipour A, Andersson JO, Sicheritz-Ponten T, Alsmark UC, Podowski RM, Naslund AK, Eriksson AS, Winkler HH, Kurland CG. "The genome sequence of Rickettsia prowazekii and the origin of mitochondria." Nature. 1998 Nov 12;396(6707):133-40.; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6.; [3] PubMed:338609 Satre M, Kennedy EP. "Identification of bound pyruvate essential for the activity of phosphatidylserine decarboxylase of Escherichia coli." J Biol Chem. 1978 Jan 25;253(2):479-83. Update 2003/08/19. // Entry E0402 Definition [Rickettsia prowazekii; Rickettsia conorii.] Zinc [cpd:C00038] (ET=TNC); Manganese [cpd:C00034] (ET=TN) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for zinc/manganese (TransportDB [1]). Delta-aminolevulinic acid dehydratase (HemB) [EC:4.2.1.24] present in Rickettsia requires zinc as a cofactor[2,3]. Hypothesis IN=cpd:C00038, Zinc, ET=TNC; IN=cpd:C00034, Manganese, ET=TN. Gene RC0014; RC0964; RC1289; RP539; RC0798. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:2464127 Echelard Y, Dymetryszyn J, Drolet M, Sasarman A. "Nucleotide sequence of the hemB gene of Escherichia coli K12." Mol Gen Genet. 1988 Nov;214(3):503-8. ; [3] PubMed:9287008 Chauhan S, Titus DE, O'Brian MR. "Metals control activity and expression of the heme biosynthesis enzyme delta-aminolevulinic acid dehydratase in Bradyrhizobium japonicum." J Bacteriol. 1997 Sep;179(17):5516-20. Update 2003/08/19. // Entry E0403 Definition [Rickettsia prowazekii; Rickettsia conorii.] L-Glutamine [cpd:C00064] (ET=GT) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for glutamine (TransportDB [1]). Hypothesis IN=cpd:C00064, L-Glutamine, ET=GT. Gene RC0171; RC1341. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0404 Definition [Rickettsia prowazekii; Rickettsia conorii.] Amino acid [cpd:C00045] (ET=GT) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for amino acid (TransportDB [1]). Hypothesis IN=cpd:C00045, Amino acid, ET=GT. Gene RC0192; RC1027; RC1077, RC1076. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0405 Definition [Rickettsia prowazekii; Rickettsia conorii.] L-Valine [cpd:C00183] (ET=GT); L-Leucine [cpd:C00123] (ET=GT); L-Isoleucine [cpd:C00407] (ET=GT) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for branched chain amino acid (TransportDB [1]). Hypothesis IN=cpd:C00183, L-Valine, ET=GT; IN=cpd:C00123, L-Leucine, ET=GT; IN=cpd:C00407, L-Isoleucine, ET=GT. Gene RC0658. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0406 Definition [Rickettsia prowazekii; Rickettsia conorii.] Heme [cpd:C00032] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for heme (TransportDB [1]). Hypothesis IN=cpd:C00032, Heme, ET=T. Gene RC1228. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0407 Definition [Rickettsia prowazekii; Rickettsia conorii.] H+ [cpd:C00080] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for proton, ATP synthase (TransportDB [1]). Hypothesis IN=cpd:C00080, H+, ET=T. Gene RC0024, RC0025, RC0026, RC0027; RC1234, RC1235, RC1236, RC1237, RC1238. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0409 Definition [Rickettsia prowazekii; Rickettsia conorii.] Magnesium [cpd:C00305] (ET=T); Cobalt [cpd:C00175] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for magnesium/cobalt (TransportDB [1]). Hypothesis IN=cpd:C00305, Magnesium, ET=T; IN=cpd:C00175, Cobalt, ET=T. Gene RC0943; RC0815; RC0886. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0410 Definition [Rickettsia prowazekii; Rickettsia conorii.] ATP [cpd:C00002] (ET=TG) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for ATP/ADP (TransportDB [1] and [2,3]). Hypothesis IN=cpd:C00002, ATP, ET=TG. Gene RC0081; RC0666; RC0722; RC1138. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:9823893 Andersson SG, Zomorodipour A, Andersson JO, Sicheritz-Ponten T, Alsmark UC, Podowski RM, Naslund AK, Eriksson AS, Winkler HH, Kurland CG. "The genome sequence of Rickettsia prowazekii and the origin of mitochondria." Nature. 1998 Nov 12;396(6707):133-40.; [3] PubMed:2986146 Krause DC, Winkler HH, Wood DO. "Cloning and expression of the Rickettsia prowazekii ADP/ATP translocator in Escherichia coli." Proc Natl Acad Sci U S A. 1985 May;82(9):3015-9. Update 2003/08/19. // Entry E0411 Definition [Rickettsia prowazekii; Rickettsia conorii.] Malate [cpd:C00711] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for malate (TransportDB [1]). Hypothesis IN=cpd:C00711, Malate, ET=T. Gene RC0506. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0412 Definition [Rickettsia prowazekii; Rickettsia conorii.] L-Arginine [cpd:C00062] (ET=GT); L-Lysine [cpd:C00047] (ET=GT) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for cationic amino acid (TransportDB [1]). Hypothesis IN=cpd:C00062, L-Arginine, ET=GT; IN=cpd:C00047, L-Lysine, ET=GT. Gene RC0411. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0413 Definition [Rickettsia prowazekii; Rickettsia conorii.] L-Arginine [cpd:C00062] (ET=GT); L-Ornithine [cpd:C00077] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for arginine/ornithine (TransportDB [1]). Hypothesis IN=cpd:C00062, L-Arginine, ET=GT; IN=cpd:C00077, L-Ornithine, ET=T. Gene RC0726. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0414 Definition [Rickettsia prowazekii; Rickettsia conorii.] H+ [cpd:C00080] (ET=T); L-Glutamate [cpd:C00025] (ET=GT) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for proton/glutamate (TransportDB [1]). Hypothesis IN=cpd:C00080, H+, ET=T; IN=cpd:C00025, L-Glutamate, ET=GT. Gene RC0223. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0415 Definition [Rickettsia prowazekii; Rickettsia conorii.] Dicarboxylate [cpd:C02028] (ET=T); Sodium [cpd:C01330] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for sodium/dicarboxylate (TransportDB [1]). Hypothesis IN=cpd:C02028, Dicarboxylate, ET=T; IN=cpd:C01330, Sodium, ET=T. Gene RC0275. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0417 Definition [Rickettsia prowazekii; Rickettsia conorii.] sn-Glycerol 3-phosphate [cpd:C00093] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for glycerol-3-phosphate (TransportDB [1]). Hypothesis IN=cpd:C00093, sn-Glycerol 3-phosphate, ET=T. Gene RC0082. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0418 Definition [Rickettsia prowazekii; Rickettsia conorii.] L-Proline [cpd:C00148] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for proline (osmoprotection) (TransportDB [1]). Hypothesis IN=cpd:C00148, L-Proline, ET=T. Gene RC0107; RC1048. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0419 Definition [Rickettsia prowazekii; Rickettsia conorii.] L-Proline [cpd:C00148] (ET=GT); Betaine [cpd:C00719] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for proline/betaine (TransportDB [1]). Hypothesis IN=cpd:C00148, L-Proline, ET=GT; IN=cpd:C00719, Betaine, ET=T. Gene RC0375; RC0427; RC0512; RC0889; RC0890; RC1100; RC1101; RC1170; RC1321; RC1323; RC1368. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0420 Definition [Rickettsia prowazekii; Rickettsia conorii.] Sodium [cpd:C01330] (ET=T); H+ [cpd:C00080] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for sodium/proton (TransportDB [1]). Hypothesis IN=cpd:C01330, Sodium, ET=T; IN=cpd:C00080, H+, ET=T. Gene RC1354; RC1355. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0421 Definition [Rickettsia prowazekii; Rickettsia conorii.] Sodium [cpd:C01330] (ET=T); Pantothenate [cpd:C00864] (ET=T) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for sodium/pantothenate (TransportDB [1]). Pantothenate is a precursor of coenzyme A. Rickettsia possess TCA cycle that requires CoA. (However, no enzyme has been identified that requires pantothenate.) Hypothesis IN=cpd:C01330, Sodium, ET=T; IN=cpd:C00864, Pantothenate, ET=T. Gene RC0702; RC0862. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0422 Definition [Rickettsia prowazekii; Rickettsia conorii.] Malonyl-CoA [cpd:C00083] (ET=DS); Fatty acid [cpd:C00162] (ET=GD); Fatty acid biosynthesis (path 1) [KEGG:rpr00061]; Fatty acid biosynthesis (path 2) [KEGG:rpr00062]; Fatty acid metabolism [KEGG:rpr00071]; Fatty acid biosynthesis (path 1) [KEGG:rco00061]; Fatty acid biosynthesis (path 2) [KEGG:rco00062]; Fatty acid metabolism [KEGG:rco00071] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence In fatty acid biosynthesis, acetyl-CoA carboxylase carboxyl transferase [EC:6.4.1.2] and biotin carboxylase [EC:6.3.4.14] are missing (according to KEGG [1]). Thus we may have to add malonyl-CoA. However, beta-oxidation and its reverse reactions appears to be better conserved (according to KEGG [1]). Thus Rickettsia may use exogenous fatty acids (by beta-oxidation), or synthesize fatty acids by the reverse beta-oxidation. Hypothesis IN=cpd:C00083, Malonyl-CoA, ET=DS; IN=cpd:C00162, Fatty acid, ET=GD. Gene Pathway KEGG:rpr00061 Fatty acid biosynthesis (path 1); KEGG:rpr00062 Fatty acid biosynthesis (path 2); KEGG:rpr00071 Fatty acid metabolism; KEGG:rco00061 Fatty acid biosynthesis (path 1); KEGG:rco00062 Fatty acid biosynthesis (path 2); KEGG:rco00071 Fatty acid metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0423 Definition [Rickettsia prowazekii; Rickettsia conorii.] AMP [cpd:C00020] (ET=DS); dAMP [cpd:C00360] (ET=DS); GMP [cpd:C00144] (ET=DS); dGMP [cpd:C00362] (ET=DS); Purine metabolism [KEGG:rpr00230]; Purine metabolism [KEGG:rco00230] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence There is no biosynthetic pathway for purines. Minimal requirement for the salvage pathway appears AMP or dAMP, and GMP or dGMP (according to KEGG [1]). Hypothesis IN=cpd:C00020, AMP, ET=DS; IN=cpd:C00360, dAMP, ET=DS; IN=cpd:C00144, GMP, ET=DS; IN=cpd:C00362, dGMP, ET=DS. Gene Pathway KEGG:rpr00230 Purine metabolism; KEGG:rco00230 Purine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0424 Definition [Rickettsia prowazekii; Rickettsia conorii.] Thymidine [cpd:C00214] (ET=DS); Purine metabolism [KEGG:rpr00230]; Purine metabolism [KEGG:rco00230] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence There is no biosynthetic pathway for pyrimidines. Minimal requirement for the salvage pathway appears thymidine (according to KEGG [1]). Hypothesis IN=cpd:C00214, Thymidine, ET=DS. Gene Pathway KEGG:rpr00230 Purine metabolism; KEGG:rco00230 Purine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0425 Definition [Rickettsia prowazekii; Rickettsia conorii.] Amino acid [cpd:C00045] (ET=GD); Glutamate metabolism [KEGG:rpr00251]; Glutamate metabolism [KEGG:rco00251]; Alanine and aspartate metabolism [KEGG:rpr00252]; Alanine and aspartate metabolism [KEGG:rco00252]; Glycine, serine and threonine metabolism [KEGG:rpr00260]; Glycine, serine and threonine metabolism [KEGG:rco00260]; Valine, leucine and isoleucine degradation [KEGG:rpr00280]; Valine, leucine and isoleucine degradation [KEGG:rco00280]; Lysine biosynthesis [KEGG:rpr00300]; Lysine biosynthesis [KEGG:rco00300] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Most of the biosynthetic enzymes for amino acids are absent, except several enzymes for amino acid interconversion ([1] and according to KEGG [2]). It is highly likely that Rickettsia uptake most of 20 amino acids from hosts. Some enzymes relevant to amino acid metabolisms are as follows. AatA, aspartate aminotransferase A [EC:2.6.1.1], converts aspartate into glutamate. GlyA, serine hydroxymethyltransferase [EC:2.1.2.1], converts serine (with the use of tetrahydrofolate) into glycine. According to [1], the importance of tetrahydrofolate metabolism for Rickettsia may explain the presence of GlyA. TdcB, threonine dehydratase [EC:4.3.1.19], converts threonine into 2-oxobutanoate and or converts serine into pyruvate. From glycine, HemA, 5-aminolevulinic acid synthase [EC:2.3.1.37], continues to the synthesis of porphyrin. From aspartate, there is initial steps for lysine biosynthesis, which lacks the last step ([EC:4.1.1.20]), and supposed to be the pathway for diaminopimelate (for peptidoglycan) [1]. IlvE, branched-chain amino acid aminotransferase [EC:2.6.1.42], converts leucine, isoleucine and valine into glutamate. Hypothesis IN=cpd:C00045, Amino acid, ET=GD. Gene Pathway KEGG:rpr00251 Glutamate metabolism; KEGG:rco00251 Glutamate metabolism; KEGG:rpr00252 Alanine and aspartate metabolism; KEGG:rco00252 Alanine and aspartate metabolism; KEGG:rpr00260 Glycine, serine and threonine metabolism; KEGG:rco00260 Glycine, serine and threonine metabolism; KEGG:rpr00280 Valine, leucine and isoleucine degradation; KEGG:rco00280 Valine, leucine and isoleucine degradation; KEGG:rpr00300 Lysine biosynthesis; KEGG:rco00300 Lysine biosynthesis. Reference [1] PubMed:9823893 Andersson SG, Zomorodipour A, Andersson JO, Sicheritz-Ponten T, Alsmark UC, Podowski RM, Naslund AK, Eriksson AS, Winkler HH, Kurland CG. "The genome sequence of Rickettsia prowazekii and the origin of mitochondria." Nature. 1998 Nov 12;396(6707):133-40.; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0426 Definition [Rickettsia prowazekii; Rickettsia conorii.] D-Glutamate [cpd:C00217] (ET=DS); D-Glutamine and D-glutamate metabolism [KEGG:rpr00471]; D-Glutamine and D-glutamate metabolism [KEGG:rco00471] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Initial step of peptidoglycan synthesis pathway requires D-glutamate, which is generated by glutamate racemase [EC:5.1.1.3]. Rickettsia lacks this enzyme. Thus they might uptake D-glutamate from hosts. (It is not clear if MurD [EC:6.3.2.9] can use L-glutamate in spite of D-glutamate. (According to KEGG [1]). Hypothesis IN=cpd:C00217, D-Glutamate, ET=DS. Gene Pathway KEGG:rpr00471 D-Glutamine and D-glutamate metabolism; KEGG:rco00471 D-Glutamine and D-glutamate metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0427 Definition [Rickettsia prowazekii; Rickettsia conorii.] Glutathione [cpd:C00051] (ET=DS); Glutathione metabolism [KEGG:rpr00480]; Glutathione metabolism [KEGG:rco00480] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Rickettsia appear to lack the biosynthetic pathway for glutathione (according to KEGG [1]). However glutathione S-transferase [EC:2.5.1.18] is present. Hypothesis IN=cpd:C00051, Glutathione, ET=DS. Gene Pathway KEGG:rpr00480 Glutathione metabolism; KEGG:rco00480 Glutathione metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0428 Definition [Rickettsia prowazekii; Rickettsia conorii.] 1-Acyl-sn-glycerol 3-phosphate [cpd:C00681] (ET=U); Phosphatidate [cpd:C00416] (ET=DS); Glycerolipid metabolism [KEGG:rpr00561]; Glycerolipid metabolism [KEGG:rco00561] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Phosphatidylglycerol is a major phospholipid in a cell. The lack of glycerol-3-phosphate O-acyltransferase [EC:2.3.1.15] in Rickettsia (according to KEGG [1]) suggests the requirement for 1-acyl-sn-glycerol 3-phosphate or phosphatidate as a neutrient to acquire phosphatidylglycerol. An Escherichia coli mutant with a deficient glycerol-3-phosphate acyltransferase (because of a high Km value) is known to require sn-glycerol-3-phosphate for growth (glycerol-P auxotroph) [2]. Hypothesis IN=cpd:C00681, 1-Acyl-sn-glycerol 3-phosphate, ET=U; IN=cpd:C00416, Phosphatidate, ET=DS. Gene Pathway KEGG:rpr00561 Glycerolipid metabolism; KEGG:rco00561 Glycerolipid metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6.; [2] PubMed:240816 Bell RM. "Mutants of Escherichia coli defective in membrane phospholipid synthesis." J Biol Chem. 1975 Sep 25;250(18):7147-52. Update 2003/09/12. // Entry E0429 Definition [Rickettsia prowazekii; Rickettsia conorii.] NAD+ [cpd:C00003] (ET=DS); Nicotinate and nicotinamide metabolism [KEGG:rpr00760]; Nicotinate and nicotinamide metabolism [KEGG:rco00760] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence No biosynthetic pathway for NAD+, which enters into the TCA cycle (according to KEGG [1]). Hypothesis IN=cpd:C00003, NAD+, ET=DS. Gene Pathway KEGG:rpr00760 Nicotinate and nicotinamide metabolism; KEGG:rco00760 Nicotinate and nicotinamide metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0430 Definition [Rickettsia prowazekii; Rickettsia conorii.] CoA [cpd:C00010] (ET=DS); Pantothenate and CoA biosynthesis [KEGG:rpr00770]; Pantothenate and CoA biosynthesis [KEGG:rco00770] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence No biosynthetic pathway for coenzyme A (CoA) (according to KEGG [1]), which is required for TCA cycle of Rickettsia. Hypothesis IN=cpd:C00010, CoA, ET=DS. Gene Pathway KEGG:rpr00770 Pantothenate and CoA biosynthesis; KEGG:rco00770 Pantothenate and CoA biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0431 Definition [Rickettsia prowazekii; Rickettsia conorii.] Biotin [cpd:C00120] (ET=DC); Biotin metabolism [KEGG:rpr00780]; Biotin metabolism [KEGG:rco00780] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence No biosynthetic pathway for biotin (according to KEGG [1]). A metabolism check system (under development, H. Ogata) suggests Rickettsia require biotin for thier propionyl-CoA carboxylase [EC:6.4.1.3]. Hypothesis IN=cpd:C00120, Biotin, ET=DC. Gene RC0959; RC0960; RP618; RP619. Pathway KEGG:rpr00780 Biotin metabolism; KEGG:rco00780 Biotin metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0432 Definition [Rickettsia prowazekii; Rickettsia conorii.] Folic acid [cpd:C00504] (ET=DS); Tetrahydrofolate [cpd:C00101] (ET=DS); Folate biosynthesis [KEGG:rpr00790]; Folate biosynthesis [KEGG:rco00790] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence No biosynthetic pathway for folate but there are some enzymes for the folate metabolism (according to KEGG [1]). We may add in the medium folate (vitamin form) or tetrahydrofolate (coenzyme form). Tetrahydrofolate transfer C1 (one carbon) units and generally required for the synthesis of thymine, purine bases, serine, methionine and pantothenate. Hypothesis IN=cpd:C00504, Folic acid, ET=DS; IN=cpd:C00101, Tetrahydrofolate, ET=DS. Gene Pathway KEGG:rpr00790 Folate biosynthesis; KEGG:rco00790 Folate biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0433 Definition [Rickettsia prowazekii; Rickettsia conorii.] Protoporphyrin [cpd:C02191] (ET=D); Heme [cpd:C00032] (ET=D); Porphyrin and chlorophyll metabolism [KEGG:rpr00860]; Porphyrin and chlorophyll metabolism [KEGG:rco00860] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Biosynthetic pathway of heme lacks two enzymes, HemD [EC:4.2.1.75] and HemYG [EC:1.3.3.4] (according to KEGG [1]). If the lack of these enzymes is significant, we may have to add protoporphyrin or heme. Hypothesis IN=cpd:C02191, Protoporphyrin, ET=D; IN=cpd:C00032, Heme, ET=D. Gene Pathway KEGG:rpr00860 Porphyrin and chlorophyll metabolism; KEGG:rco00860 Porphyrin and chlorophyll metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0434 Definition [Rickettsia prowazekii; Rickettsia conorii.] Ubiquinone [cpd:C00399] (ET=D); Chorismate [cpd:C00251] (ET=DS); Ubiquinone biosynthesis [KEGG:rpr00130]; Ubiquinone biosynthesis [KEGG:rco00130] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Ubiquinone synthetic pathway is partially conserved, but the synthetic pathway for the initial compound chorismate appears absent (according to KEGG [1]). Missing enzymes are UbiC, UbiB and UbiF. Hypothesis IN=cpd:C00399, Ubiquinone, ET=D; IN=cpd:C00251, Chorismate, ET=DS. Gene Pathway KEGG:rpr00130 Ubiquinone biosynthesis; KEGG:rco00130 Ubiquinone biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0435 Definition [Rickettsia prowazekii; Rickettsia conorii.] S-Adenosyl-L-methionine [cpd:C00019] (ET=DT) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Presence of transporters for S-adenosylmethionine (AdoMet) [1], and the lack (pseudogene status) of AdoMet synthetase, MetK, in Rickettsia [2,3,4]. AdoMet is an important substrate for methyltransferase reaction in the cell. Hypothesis IN=cpd:C00019, S-Adenosyl-L-methionine, ET=DT. Gene RP076; RC0106. Pathway Reference [1] PubMed:12730161 Tucker AM, Winkler HH, Driskell LO, Wood DO. "S-adenosylmethionine transport in Rickettsia prowazekii." J Bacteriol. 2003 May;185(10):3031-5.; [2] PubMed:9823893 Andersson SG, Zomorodipour A, Andersson JO, Sicheritz-Ponten T, Alsmark UC, Podowski RM, Naslund AK, Eriksson AS, Winkler HH, Kurland CG. "The genome sequence of Rickettsia prowazekii and the origin of mitochondria." Nature. 1998 Nov 12;396(6707):133-40.; [3] PubMed:11557893 Ogata H, Audic S, Renesto-Audiffren P, Fournier PE, Barbe V, Samson D, Roux V, Cossart P, Weissenbach J, Claverie JM, Raoult D. "Mechanisms of evolution in Rickettsia conorii and R. prowazekii." Science. 2001 Sep 14;293(5537):2093-8.; [4] PubMed:10486973 Andersson JO, Andersson SG. "Genome degradation is an ongoing process in Rickettsia." Mol Biol Evol. 1999 Sep;16(9):1178-91. Update 2003/08/19. // Entry E0436 Definition [Rickettsia prowazekii; Rickettsia conorii.] NH3 [cpd:C00014] (ET=U) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Rickettsia may have two-component system for nitrogen assimilation (NtrX/NtrY) (according to KEGG [1]). Hypothesis IN=cpd:C00014, NH3, ET=U. Gene Pathway Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0437 Definition [Rickettsia prowazekii; Rickettsia conorii.] FMN [cpd:C00061] (ET=DC); FAD [cpd:C00016] (ET=DC); Magnesium [cpd:C00305] (ET=NC); Manganese [cpd:C00034] (ET=NC); Calcium [cpd:C00076] (ET=NC); Riboflavin metabolism [KEGG:map00740]; Pyrimidine metabolism [KEGG:rco00240]; Pyrimidine metabolism [KEGG:rpr00240]; Sterol biosynthesis [KEGG:map00100] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Rickettsia have isopentenyl-diphosphate D-isomerase [EC:5.3.3.2] [1,2], which uses FMN or FAD, and Magnesium or Manganese or Calcium, as cofactors [3]. Rickettsia also have thymidylate synthase (ThyX), which uses reduced flavin nucleotides [4]. However, Rickettsia do not have enzymes for riboflavin metabolism (according to KEGG [5]). Hypothesis IN=cpd:C00061, FMN, ET=DC; IN=cpd:C00016, FAD, ET=DC; IN=cpd:C00305, Magnesium, ET=NC; IN=cpd:C00034, Manganese, ET=NC; IN=cpd:C00076, Calcium, ET=NC. Gene RC0744; RP452; RC0405; RP301. Pathway KEGG:map00740 Riboflavin metabolism; KEGG:rco00240 Pyrimidine metabolism; KEGG:rpr00240 Pyrimidine metabolism; KEGG:map00100 Sterol biosynthesis. Reference [1] PubMed:9823893 Andersson SG, Zomorodipour A, Andersson JO, Sicheritz-Ponten T, Alsmark UC, Podowski RM, Naslund AK, Eriksson AS, Winkler HH, Kurland CG. "The genome sequence of Rickettsia prowazekii and the origin of mitochondria." Nature. 1998 Nov 12;396(6707):133-40.; [2] PubMed:11557893 Ogata H, Audic S, Renesto-Audiffren P, Fournier PE, Barbe V, Samson D, Roux V, Cossart P, Weissenbach J, Claverie JM, Raoult D. "Mechanisms of evolution in Rickettsia conorii and R. prowazekii." Science. 2001 Sep 14;293(5537):2093-8.; [3] PubMed:11158573 Kaneda K, Kuzuyama T, Takagi M, Hayakawa Y, Seto H. "An unusual isopentenyl diphosphate isomerase found in the mevalonate pathway gene cluster from Streptomyces sp. strain CL190." Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):932-7. Epub 2001 Jan 23. ; [4] PubMed:12029065 Myllykallio H, Lipowski G, Leduc D, Filee J, Forterre P, Liebl U. "An alternative flavin-dependent mechanism for thymidylate synthesis." Science. 2002 Jul 5;297(5578):105-7. Epub 2002 May 23. ; [5] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0438 Definition [Rickettsia prowazekii; Rickettsia conorii.] Heme [cpd:C00032] (ET=DC); Copper [cpd:C00070] (ET=NC); Zinc [cpd:C00038] (ET=NC); Magnesium [cpd:C00305] (ET=NC); Sodium [cpd:C01330] (ET=NC) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence The assembly of cytochrome c oxidase [EC:1.9.3.1] is dependent on the insertion of five types of cofactors, including two hemes, three copper ions, and one Zn, Mg, and Na ion [1]. Heme may not be synthesized in Rickettsia (according to KEGG [2]). Hypothesis IN=cpd:C00032, Heme, ET=DC; IN=cpd:C00070, Copper, ET=NC; IN=cpd:C00038, Zinc, ET=NC; IN=cpd:C00305, Magnesium, ET=NC; IN=cpd:C01330, Sodium, ET=NC. Gene Pathway Reference [1] PubMed:12755640 Carr HS, Winge DR. "Assembly of cytochrome c oxidase within the mitochondrion." Acc Chem Res. 2003 May;36(5):309-16. Review. ; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0439 Definition [Rickettsia prowazekii; Rickettsia conorii.] dipyrromethane (ET=C) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Porphobilinogen deaminase (HemC) [EC:4.3.1.8] requires dipyrromethane as a cofactor [1-3]. Hypothesis IN=dipyrromethane, ET=C. Gene RP466; RC0706. Pathway Reference [1] PubMed:9766005 McNeill LA, Shoolingin-Jordan PM. "Dipyrromethane cofactor assembly in porphobilinogen deaminase." Biochem Soc Trans. 1998 Aug;26(3):S286. No abstract available. ; [2] PubMed:8687374 Shoolingin-Jordan PM, Warren MJ, Awan SJ. "Discovery that the assembly of the dipyrromethane cofactor of porphobilinogen deaminase holoenzyme proceeds initially by the reaction of preuroporphyrinogen with the apoenzyme." Biochem J. 1996 Jun 1;316 ( Pt 2):373-6. ; [3] PubMed:1522882 Louie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Warren MJ, Woodcock SC, Jordan PM. "Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site." Nature. 1992 Sep 3;359(6390):33-9. Update 2003/08/25. // Entry E0440 Definition [Rickettsia prowazekii; Rickettsia conorii.] Iron [cpd:C00023] (ET=NC); Iron-sulfur [cpd:C00824] (ET=NC) Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Superoxide dismutase [EC:1.15.1.1] uses iron as a cofactor [1,2], and aconitate hydratase [EC:4.2.1.3] uses iron-sulfur as a cofactor [3]. Hypothesis IN=cpd:C00023, Iron, ET=NC; IN=cpd:C00824, Iron-sulfur, ET=NC. Gene RP535; RC0778; RP799; RC1233. Pathway Reference [1] PubMed:2669953 Beyer WF Jr, Reynolds JA, Fridovich I. "Differences between the manganese- and the iron-containing superoxide dismutases of Escherichia coli detected through sedimentation equilibrium, hydrodynamic, and spectroscopic studies." Biochemistry. 1989 May 16;28(10):4403-9. ; [2] PubMed:10419947 Santos R, Bocquet S, Puppo A, Touati D. "Characterization of an atypical superoxide dismutase from Sinorhizobium meliloti." J Bacteriol. 1999 Aug;181(15):4509-16. ; [3] PubMed:10585860 Jordan PA, Tang Y, Bradbury AJ, Thomson AJ, Guest JR. "Biochemical and spectroscopic characterization of Escherichia coli aconitases (AcnA and AcnB)." Biochem J. 1999 Dec 15;344 Pt 3:739-46. Update 2003/08/25. // Entry E0441 Definition [Rickettsia prowazekii; Rickettsia conorii.] Pyridoxal phosphate [cpd:C00018] (ET=DC); Pyridoxine [cpd:C00314] (ET=DV); Vitamin B6 metabolism [KEGG:map00750] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Threonine dehydratase (TdcB) [EC:4.3.1.19] uses pyridoxal phosphate as a cofactor [1,2]. There is no metabolic pathway for vitamin B6, including pyridoxal phosphate (according to KEGG [3]). Pyridoxine (vitamin form) and pyridoxal phosphate are generally involved in transamination, deamination, decarboxylation and racemation of amino acids. Hypothesis IN=cpd:C00018, Pyridoxal phosphate, ET=DC; IN=cpd:C00314, Pyridoxine, ET=DV. Gene RP449; RC0628. Pathway KEGG:map00750 Vitamin B6 metabolism. Reference [1] PubMed:9562556 Gallagher DT, Gilliland GL, Xiao G, Zondlo J, Fisher KE, Chinchilla D, Eisenstein E. "Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase." Structure. 1998 Apr 15;6(4):465-75. ; [2] PubMed:8112347 Alexander FW, Sandmeier E, Mehta PK, Christen P. "Evolutionary relationships among pyridoxal-5'-phosphate-dependent enzymes. Regio-specific alpha, beta and gamma families." Eur J Biochem. 1994 Feb 1;219(3):953-60. ; [3] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0442 Definition [Rickettsia prowazekii; Rickettsia conorii.] Thiamin [cpd:C00378] (ET=DV); Thiamin diphosphate [cpd:C00068] (ET=DC); Thiamine metabolism [KEGG:map00730] Organism Rickettsia prowazekii (TAX:782 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; typhus group) - Rickettsia conorii (TAX:781 Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Rickettsiaceae; Rickettsieae; Rickettsia; spotted fever group). Evidence Pyruvate dehydrogenase complex E1 component [EC:1.2.4.1] requires thiamine diphosphate as a cofactor [1], but Rickettsia do not have biosynthetic pathway for thiamine diphosphate (according to KEGG [2]). Hypothesis IN=cpd:C00378, Thiamin, ET=DV; IN=cpd:C00068, Thiamin diphosphate, ET=DC. Gene RP261, RP262; RC0347, RC0348; Pathway KEGG:map00730 Thiamine metabolism. Reference [1] PubMed:8969175 Yi J, Nemeria N, McNally A, Jordan F, Machado RS, Guest JR. "Effect of substitutions in the thiamin diphosphate-magnesium fold on the activation of the pyruvate dehydrogenase complex from Escherichia coli by cofactors and substrate." J Biol Chem. 1996 Dec 27;271(52):33192-200. ; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // # # Evidence-Hypothesis Database for Tropheryma whipplei. # Entry E0601 Definition [Tropheryma whipplei.] Polysaccharide [cpd:C00420] (ET=T) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for polysaccharide (TransportDB [1]). Hypothesis IN=cpd:C00420, Polysaccharide, ET=T. Gene TW038, TW039. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0602 Definition [Tropheryma whipplei.] Fe(III)dicitrate [cpd:C06229] (ET=T) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for iron(III) dicitrate (TransportDB [1]). Hypothesis IN=cpd:C06229, Fe(III)dicitrate, ET=T. Gene TW068, TW069, TW070, TW066, TW067. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0603 Definition [Tropheryma whipplei.] Oligopeptide [cpd:C00098] (ET=T); Peptide [cpd:C00012] (ET=T); Dipeptide [cpd:C00107] (ET=T) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for oligopeptide and dipeptide (TransportDB [1]). Hypothesis IN=cpd:C00098, Oligopeptide, ET=T; IN=cpd:C00012, Peptide, ET=T; IN=cpd:C00107, Dipeptide, ET=T. Gene TW145, TW146; TW151, TW149, TW150. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0604 Definition [Tropheryma whipplei.] Cobalt [cpd:C00175] (ET=CNT); NAD+ [cpd:C00003] (ET=CT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for cobalt ion (TransportDB [1]). 3-dehydroquinate synthase [EC:4.2.3.4] uses cobalt and NAD as cofactors [2,3]. Hypothesis IN=cpd:C00175, Cobalt, ET=CNT; IN=cpd:C00003, NAD+, ET=CT. Gene TW148, TW147; TWT370; TW399. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:2514789 Bender SL, Mehdi S, Knowles JR. "Dehydroquinate synthase: the role of divalent metal cations and of nicotinamide adenine dinucleotide in catalysis." Biochemistry. 1989 Sep 19;28(19):7555-60. ; [3] PubMed:8037684 Moore JD, Coggins JR, Virden R, Hawkins AR. "Efficient independent activity of a monomeric, monofunctional dehydroquinate synthase derived from the N-terminus of the pentafunctional AROM protein of Aspergillus nidulans." Biochem J. 1994 Jul 1;301 ( Pt 1):297-304. Update 2003/08/19. // Entry E0605 Definition [Tropheryma whipplei.] L-Valine [cpd:C00183] (ET=GT); L-Leucine [cpd:C00123] (ET=GT); L-Isoleucine [cpd:C00407] (ET=GT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for branched chain amino acid (TransportDB [1]). Hypothesis IN=cpd:C00183, L-Valine, ET=GT; IN=cpd:C00123, L-Leucine, ET=GT; IN=cpd:C00407, L-Isoleucine, ET=GT. Gene TW203, TW204, TW201, TW202, TW200. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0606 Definition [Tropheryma whipplei.] Orthophosphate [cpd:C00009] (ET=NT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for phosphate ion (TransportDB [1]). Hypothesis IN=cpd:C00009, Orthophosphate, ET=NT. Gene TW415, TW418, TW416, TW417. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0607 Definition [Tropheryma whipplei.] Sugar [cpd:C11477] (ET=T) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for sugar (TransportDB [1]). Hypothesis IN=cpd:C11477, Sugar, ET=T. Gene TW441, TW442, TW443; TW096. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0608 Definition [Tropheryma whipplei.] Cation [cpd:C01373] (ET=NT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for metal cation (TransportDB [1]). Hypothesis IN=cpd:C01373, Cation, ET=NT. Gene TW773. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0609 Definition [Tropheryma whipplei.] H+ [cpd:C00080] (ET=NT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for proteins, by ATP synthase (TransportDB [1]). Hypothesis IN=cpd:C00080, H+, ET=NT. Gene TW338, TW339, TW340, TW341, TW342, TW343, TW344, TW345. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0610 Definition [Tropheryma whipplei.] Copper [cpd:C00070] (ET=NT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for copper ion (TransportDB [1]). Hypothesis IN=cpd:C00070, Copper, ET=NT. Gene TW813. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0611 Definition [Tropheryma whipplei.] D-Galactonate [cpd:C00880] (ET=T) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for D-galactonate (TransportDB [1]). Hypothesis IN=cpd:C00880, D-Galactonate, ET=T. Gene TW667. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0612 Definition [Tropheryma whipplei.] Sodium [cpd:C01330] (ET=NT); H+ [cpd:C00080] (ET=NT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for sodium/proton (TransportDB [1]). Hypothesis IN=cpd:C01330, Sodium, ET=NT; IN=cpd:C00080, H+, ET=NT. Gene TW795. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0613 Definition [Tropheryma whipplei.] Magnesium [cpd:C00305] (ET=CNT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for magnesium (TransportDB [1]). Enolase [EC:4.2.1.11] uses magnesium as a cofactor [2]. Hypothesis IN=cpd:C00305, Magnesium, ET=CNT. Gene TW237; TWT783; TW793. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:8994873 Reed GH, Poyner RR, Larsen TM, Wedekind JE, Rayment I. "Structural and mechanistic studies of enolase." Curr Opin Struct Biol. 1996 Dec;6(6):736-43. Review. Update 2003/08/19. // Entry E0614 Definition [Tropheryma whipplei.] Iron [cpd:C00023] (ET=NT) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporters for iron (TransportDB [1]). Hypothesis IN=cpd:C00023, Iron, ET=NT. Gene TW163, TW162; TW685, TW686, TW687. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0622 Definition [Tropheryma whipplei.] D-Glucose [cpd:C00031] (ET=S); Glycolysis / Gluconeogenesis [KEGG:twh00010]; Pentose phosphate pathway [KEGG:twh00030]; Citrate cycle (TCA cycle) [KEGG:twh00020] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence T. whipplei has glycolysis (bypassed by pentose phosphate pathway) but lacks TCA cycle (according to KEGG [1]). Thus glucose is a primary energy source. Hypothesis IN=cpd:C00031, D-Glucose, ET=S. Gene Pathway KEGG:twh00010 Glycolysis / Gluconeogenesis; KEGG:twh00030 Pentose phosphate pathway; KEGG:twh00020 Citrate cycle (TCA cycle). Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0624 Definition [Tropheryma whipplei.] D-Mannose 6-phosphate [cpd:C00275] (ET=S); D-Mannose [cpd:C00159] (ET=S); Fructose and mannose metabolism [KEGG:twh00051] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Mannose metabolism indicates the use of mannose (or mannose-6P) (according to KEGG [1]). Hypothesis IN=cpd:C00275, D-Mannose 6-phosphate, ET=S; IN=cpd:C00159, D-Mannose, ET=S. Gene Pathway KEGG:twh00051 Fructose and mannose metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0625 Definition [Tropheryma whipplei.] Malonyl-CoA [cpd:C00083] (ET=SD); [KEGG: twh00620]; Fatty acid biosynthesis (path 1) [KEGG:twh00061] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Malonyl-CoA cannot be synthesized from pyruvate (according to KEGG [1]). Malonyl-CoA is the methylene donor in the fatty acid biosynthesis. T. whipplei also lacks acetyl-CoA carboxylase [EC:6.4.1.2] in the fatty acid biosynthesis. Hypothesis IN=cpd:C00083, Malonyl-CoA, ET=SD. Gene Pathway KEGG: twh00620 ; KEGG:twh00061 Fatty acid biosynthesis (path 1). Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0626 Definition [Tropheryma whipplei.] Vitamin K [cpd:C01628] (ET=U); alpha-Tocopherol [cpd:C02477] (ET=U); trans,trans-Farnesyl diphosphate [cpd:C00448] (ET=U); Geranylgeranyl diphosphate [cpd:C00353] (ET=U); Phytoene [cpd:C05413] (ET=U); Sterol biosynthesis [KEGG:twh00100] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence T. whipplei has a pathway from the glycolysis to isopentenyl-PP. Required final products after this pathway is not obvious. A comparison with the M. tuberculosis pathways suggests that vitamin K, vitamin E, fanesyl-PP, all-trans-geranylgeranyl diphosphate, phytoene could be important molecules. Vitamin K (which includes menaquinone) functions in electron transfer. Vitamin E stabilizes membrane structures through anti-oxidation property. (According to KEGG [1]). Hypothesis IN=cpd:C01628, Vitamin K, ET=U; IN=cpd:C02477, alpha-Tocopherol, ET=U; IN=cpd:C00448, trans,trans-Farnesyl diphosphate, ET=U; IN=cpd:C00353, Geranylgeranyl diphosphate, ET=U; IN=cpd:C05413, Phytoene, ET=U. Gene Pathway KEGG:twh00100 Sterol biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0627 Definition [Tropheryma whipplei.] Adenine [cpd:C00147] (ET=S); Guanine [cpd:C00242] (ET=S); Purine metabolism [KEGG:twh00230] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Biosynthetic pathway for purines is complete. Salvage pathway may utilize adenine and guanine (according to KEGG [1]). Hypothesis IN=cpd:C00147, Adenine, ET=S; IN=cpd:C00242, Guanine, ET=S. Gene Pathway KEGG:twh00230 Purine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0628 Definition [Tropheryma whipplei.] Thymidine [cpd:C00214] (ET=S); UMP [cpd:C00105] (ET=S); CMP [cpd:C00055] (ET=S); dCMP [cpd:C00239] (ET=S); Pyrimidine metabolism [KEGG:twh00240] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Biosynthetic pathway for pyrimidine is complete. Salvage pathway may utilize thymidine, UMP, CMP, dCMP (according to KEGG [1]). Hypothesis IN=cpd:C00214, Thymidine, ET=S; IN=cpd:C00105, UMP, ET=S; IN=cpd:C00055, CMP, ET=S; IN=cpd:C00239, dCMP, ET=S. Gene Pathway KEGG:twh00240 Pyrimidine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0629 Definition [Tropheryma whipplei.] D-Glucose 1-phosphate [cpd:C00103] (ET=SD); Nucleotide sugars metabolism [KEGG:twh00520] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence T. whipplei has a pathway from glucose-1P to GDP-L-rhamnose and dTDP-L-rhamnose but appears to lack the pathway leading to glucose-1P (according to KEGG [1]). Hypothesis IN=cpd:C00103, D-Glucose 1-phosphate, ET=SD. Gene Pathway KEGG:twh00520 Nucleotide sugars metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0630 Definition [Tropheryma whipplei.] L-Histidine [cpd:C00135] (ET=GD); L-Tryptophan [cpd:C00078] (ET=GD); L-Leucine [cpd:C00123] (ET=GD); L-Arginine [cpd:C00062] (ET=GD); L-Proline [cpd:C00148] (ET=GD); L-Lysine [cpd:C00047] (ET=GD); L-Methionine [cpd:C00073] (ET=GD); L-Cysteine [cpd:C00097] (ET=GD); L-Asparagine [cpd:C00152] (ET=GD); L-Glutamate [cpd:C00025] (ET=GD); Glutamine [cpd:C00303] (ET=GD); L-Phenylalanine [cpd:C00079] (ET=GD); Glutamate metabolism [KEGG:twh00251]; Alanine and aspartate metabolism [KEGG:twh00252]; Glycine, serine and threonine metabolism [KEGG:twh00260]; Methionine metabolism [KEGG:twh00271]; Cysteine metabolism [KEGG:twh00272]; Valine, leucine and isoleucine degradation [KEGG:twh00280]; Valine, leucine and isoleucine biosynthesis [KEGG:twh00290]; Lysine biosynthesis [KEGG:twh00300]; Lysine degradation [KEGG:twh00310]; Arginine and proline metabolism [KEGG:twh00330]; Histidine metabolism [KEGG:twh00340]; Tyrosine metabolism [KEGG:twh00350]; Tryptophan metabolism [KEGG:twh00380]; Phenylalanine, tyrosine and tryptophan biosynthesis [KEGG:twh00400] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Amino acid metabolism has been analyzed ([1,2] and according to KEGG [3]). The pathways were entirely missing (absence of genes) for nine amino acids (histidine, tryptophan, leucine, arginine, proline, lysine, methionine, cysteine and asparagine). In addition, de novo synthesis of glutamate and glutamine was impossible due to the absence of the TCA-cycle (2-oxoglutarate). As a consequence the glutamate-dependent biosyntheses of aspartate, threonine, valine, isoleucine become impossible. Finally, PheA, an enzyme for phenylalanine synthesis is also missing. These suggested that T. whipplei acquires amino acids or precursors from its host, through membrane transport systems. Hypothesis IN=cpd:C00135, L-Histidine, ET=GD; IN=cpd:C00078, L-Tryptophan, ET=GD; IN=cpd:C00123, L-Leucine, ET=GD; IN=cpd:C00062, L-Arginine, ET=GD; IN=cpd:C00148, L-Proline, ET=GD; IN=cpd:C00047, L-Lysine, ET=GD; IN=cpd:C00073, L-Methionine, ET=GD; IN=cpd:C00097, L-Cysteine, ET=GD; IN=cpd:C00152, L-Asparagine, ET=GD; IN=cpd:C00025, L-Glutamate, ET=GD; IN=cpd:C00303, Glutamine, ET=GD; IN=cpd:C00079, L-Phenylalanine, ET=GD. Gene Pathway KEGG:twh00251 Glutamate metabolism; KEGG:twh00252 Alanine and aspartate metabolism; KEGG:twh00260 Glycine, serine and threonine metabolism; KEGG:twh00271 Methionine metabolism; KEGG:twh00272 Cysteine metabolism; KEGG:twh00280 Valine, leucine and isoleucine degradation; KEGG:twh00290 Valine, leucine and isoleucine biosynthesis; KEGG:twh00300 Lysine biosynthesis; KEGG:twh00310 Lysine degradation; KEGG:twh00330 Arginine and proline metabolism; KEGG:twh00340 Histidine metabolism; KEGG:twh00350 Tyrosine metabolism; KEGG:twh00380 Tryptophan metabolism; KEGG:twh00400 Phenylalanine, tyrosine and tryptophan biosynthesis. Reference [1] PubMed:12902375 Raoult D, Ogata H, Audic S, Robert C, Suhre K, Drancourt M, Claverie JM. "Tropheryma whipplei twist: a human pathogenic actinobacteria with a reduced genome." Genome Res. 2003 Aug;13(8):1800-9.; [2] PubMed:12606174 Bentley SD, Maiwald M, Murphy LD, Pallen MJ, Yeats CA, Dover LG, Norbertczak HT, Besra GS, Quail MA, Harris DE, von Herbay A, Goble A, Rutter S, Squares R, Squares S, Barrell BG, Parkhill J, Relman DA. "Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei." Lancet. 2003 Feb 22;361(9358):637-44.; [3] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0631 Definition [Tropheryma whipplei.] beta-Alanine [cpd:C00099] (ET=SD); (R)-Pantoate [cpd:C00522] (ET=SD); beta-Alanine metabolism [KEGG:twh00410]; Pantothenate and CoA biosynthesis [KEGG:twh00770] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Beta-alanine is used to produce pantothenate, which is in turn used for coenzyme A (CoA) synthesis. T. whipplei does not have synthetic pathway for beta-alanine. In addition, in the CoA synthesis, the enzyme [EC:1.1.1.169] is missing (according to KEGG [1]). Thus T. whipplei may start CoA synthesis from beta-alanine or pantoate. Hypothesis IN=cpd:C00099, beta-Alanine, ET=SD; IN=cpd:C00522, (R)-Pantoate, ET=SD. Gene Pathway KEGG:twh00410 beta-Alanine metabolism; KEGG:twh00770 Pantothenate and CoA biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0633 Definition [Tropheryma whipplei.] D-Glutamate [cpd:C00217] (ET=SD); D-Glutamine and D-glutamate metabolism [KEGG:twh00471] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence T. whipplei does not have glutamate racemase (according to KEGG [1]). D-glutamate appears important for peptidoglycan synthesis. Hypothesis IN=cpd:C00217, D-Glutamate, ET=SD. Gene Pathway KEGG:twh00471 D-Glutamine and D-glutamate metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0634 Definition [Tropheryma whipplei.] N-Acetyl-D-glucosamine 1-phosphate [cpd:C04256] (ET=SD); UDP-N-acetyl-D-glucosamine [cpd:C00043] (ET=SD); Aminosugars metabolism [KEGG:twh00530] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence T. whipplei may use N-acetyl-D-glucosamine-1P or UDP-N-acetyl-D-glucosamine for lipopolysaccharides and peptidoglycan biosynthesis (according to KEGG [1]). Hypothesis IN=cpd:C04256, N-Acetyl-D-glucosamine 1-phosphate, ET=SD; IN=cpd:C00043, UDP-N-acetyl-D-glucosamine, ET=SD. Gene Pathway KEGG:twh00530 Aminosugars metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0635 Definition [Tropheryma whipplei.] 1-Acyl-sn-glycerol 3-phosphate [cpd:C00681] (ET=SD); Phosphatidate [cpd:C00416] (ET=SD); Glycerolipid metabolism [KEGG:twh00561] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence To generate phosphatidyl-glycero-P and/or chardiolipin, we may have to add in the medium 1-acyl-sn-glycerol-3P or phosphatidate (according to KEGG [1]). Hypothesis IN=cpd:C00681, 1-Acyl-sn-glycerol 3-phosphate, ET=SD; IN=cpd:C00416, Phosphatidate, ET=SD. Gene Pathway KEGG:twh00561 Glycerolipid metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0636 Definition [Tropheryma whipplei.] Nicotinate [cpd:C00253] (ET=VD); Nicotinamide [cpd:C00153] (ET=VD); Nicotinate and nicotinamide metabolism [KEGG:twh00760] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence There is no synthetic pathway for nicotinate or nicotinamide, which is used for synthesizing NAD+ and NADP+ (according to KEGG [1]). A metabolism check system (under development, H. Ogata) suggests that NAD+ is required for T. whipplei. Hypothesis IN=cpd:C00253, Nicotinate, ET=VD; IN=cpd:C00153, Nicotinamide, ET=VD. Gene Pathway KEGG:twh00760 Nicotinate and nicotinamide metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0637 Definition [Tropheryma whipplei.] Tetrahydrofolate [cpd:C00101] (ET=D); Folate biosynthesis [KEGG:twh00790] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Folate biosynthetic pathway lacks an enzyme dihydrofolate reductase (DHFR) ([1] and according to KEGG [2]). This missing enzyme has been considered as the target for an antibacterial agent (trimethoprim), which is used in combination with sulfamethoxazole in the treatment of Whipple's disease. If the lack of enzyme is critical in the synthesis of tetrahydrofolate, we may have to add tetrahydrofolate in the medium. Hypothesis IN=cpd:C00101, Tetrahydrofolate, ET=D. Gene Pathway KEGG:twh00790 Folate biosynthesis. Reference [1] PubMed:12788617 Cannon WR. "Whipple's disease, genomics, and drug therapy." Lancet. 2003 May 31;361(9372):1916.; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0638 Definition [Tropheryma whipplei.] Protoporphyrin [cpd:C02191] (ET=D); Heme [cpd:C00032] (ET=D); Porphyrin and chlorophyll metabolism [KEGG:twh00860] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Porphyrin (and heme) biosynthetic pathway lacks two enzymes, [EC:1.3.3.3] and [EC:1.3.3.4] (according to KEGG [1]). If the lack of enzymes is not compensated by alternative enzymes, we may have to add protoporphyrin IX or heme in the medium. Hypothesis IN=cpd:C02191, Protoporphyrin, ET=D; IN=cpd:C00032, Heme, ET=D. Gene Pathway KEGG:twh00860 Porphyrin and chlorophyll metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0639 Definition [Tropheryma whipplei.] L-Arabinose [cpd:C00259] (ET=T); D-Xylose [cpd:C00181] (ET=T) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Presence of transporter for L-arabinose/D-xylose [1]. Hypothesis IN=cpd:C00259, L-Arabinose, ET=T; IN=cpd:C00181, D-Xylose, ET=T. Gene TWT328, TWT329, TWT330. Pathway Reference [1] PubMed:12902375 Raoult D, Ogata H, Audic S, Robert C, Suhre K, Drancourt M, Claverie JM. "Tropheryma whipplei twist: a human pathogenic actinobacteria with a reduced genome." Genome Res. 2003 Aug;13(8):1800-9. Update 2003/08/19. // Entry E0640 Definition [Tropheryma whipplei.] Amino acid [cpd:C00045] (ET=E); fetal calf serum (ET=E); (T=37C) (ET=E); (CO2=5%) (ET=E) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence A successful axenic (e.g. cell-free) culture medium for T. whipplei [1] is the DMEM/F12 medium (Invitrogen Life Technologies), which is supplemented with 10% fetal calf serum, 1% L-glutamine, and 1% human non-essential amino acids, at 37 degree C in 5% carbon dioxide atmosphere. Hypothesis IN=cpd:C00045, Amino acid, ET=E; IN=fetal calf serum, ET=E; IN=(T=37C), ET=E; IN=(CO2=5%), ET=E. Gene Pathway Reference [1] PubMed:12927433 Renesto P, Crapoulet N, Ogata H, La Scola B, Vestris G, Claverie JM and Raoult D. "Genome-based design of a cell-free culture medium for Tropheryma whipplei." Lancet, 362, 447-449 (2003). Update 2003/08/19. // Entry E0641 Definition [Tropheryma whipplei.] Biotin [cpd:C00120] (ET=CD); Manganese [cpd:C00034] (ET=CN); Zinc [cpd:C00038] (ET=CN); Biotin metabolism [KEGG:map00780] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Pyruvate carboxylase [EC:6.4.1.1] requires biotin and manganese or zinc as cofactors [1]. There is no biosynthetic pathway for biotin according to KEGG [2]. Hypothesis IN=cpd:C00120, Biotin, ET=CD; IN=cpd:C00034, Manganese, ET=CN; IN=cpd:C00038, Zinc, ET=CN. Gene TW647; TWT630. Pathway KEGG:map00780 Biotin metabolism. Reference [1] PubMed:1105579 Barden RE, Taylor BL, Isoashi F, Frey WH, Zander G, Lee JC, Utter MF. "Structural properties of pyruvate carboxylases from chicken liver and other sources." Proc Natl Acad Sci U S A. 1975 Nov;72(11):4308-12. ; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0642 Definition [Tropheryma whipplei.] Heme [cpd:C00032] (ET=CD); Copper [cpd:C00070] (ET=CN); Zinc [cpd:C00038] (ET=CN); Magnesium [cpd:C00305] (ET=CN); Sodium [cpd:C01330] (ET=CN) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence The assembly of cytochrome c oxidase [EC:1.9.3.1] is dependent on the insertion of five types of cofactors, including two hemes, three copper ions, and one Zn, Mg, and Na ion [1]. Heme may not be synthesized in Tropheryma (according to KEGG [2]). Hypothesis IN=cpd:C00032, Heme, ET=CD; IN=cpd:C00070, Copper, ET=CN; IN=cpd:C00038, Zinc, ET=CN; IN=cpd:C00305, Magnesium, ET=CN; IN=cpd:C01330, Sodium, ET=CN. Gene TWT243, TWT244, TWT246. Pathway Reference [1] PubMed:12755640 Carr HS, Winge DR. "Assembly of cytochrome c oxidase within the mitochondrion." Acc Chem Res. 2003 May;36(5):309-16. Review. ; [2] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0643 Definition [Tropheryma whipplei.] dipyrromethane (ET=C) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Porphobilinogen deaminase (HemC) [EC:4.3.1.8] requires dipyrromethane as a cofactor [1-3]. Hypothesis IN=dipyrromethane, ET=C. Gene TWT732; TW746. Pathway Reference [1] PubMed:9766005 McNeill LA, Shoolingin-Jordan PM. "Dipyrromethane cofactor assembly in porphobilinogen deaminase." Biochem Soc Trans. 1998 Aug;26(3):S286. No abstract available. ; [2] PubMed:8687374 Shoolingin-Jordan PM, Warren MJ, Awan SJ. "Discovery that the assembly of the dipyrromethane cofactor of porphobilinogen deaminase holoenzyme proceeds initially by the reaction of preuroporphyrinogen with the apoenzyme." Biochem J. 1996 Jun 1;316 ( Pt 2):373-6. ; [3] PubMed:1522882 Louie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Warren MJ, Woodcock SC, Jordan PM. "Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site." Nature. 1992 Sep 3;359(6390):33-9. Update 2003/08/25. // Entry E0644 Definition [Tropheryma whipplei.] Iron [cpd:C00023] (ET=CN); Iron-sulfur [cpd:C00824] (ET=C) Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Superoxide dismutase [EC:1.15.1.1] uses iron as a cofactor [1,2], and NADH dehydrogenase [EC:1.6.99.3] uses iron-sulfur as a cofactor [3]. Hypothesis IN=cpd:C00023, Iron, ET=CN; IN=cpd:C00824, Iron-sulfur, ET=C. Gene TWT299; TW473; TWT780; TW790. Pathway Reference [1] PubMed:2669953 Beyer WF Jr, Reynolds JA, Fridovich I. "Differences between the manganese- and the iron-containing superoxide dismutases of Escherichia coli detected through sedimentation equilibrium, hydrodynamic, and spectroscopic studies." Biochemistry. 1989 May 16;28(10):4403-9. ; [2] PubMed:10419947 Santos R, Bocquet S, Puppo A, Touati D. "Characterization of an atypical superoxide dismutase from Sinorhizobium meliloti." J Bacteriol. 1999 Aug;181(15):4509-16. ; [3] PubMed:10544236 Bungert S, Krafft B, Schlesinger R, Friedrich T. "One-step purification of the NADH dehydrogenase fragment of the Escherichia coli complex I by means of Strep-tag affinity chromatography." FEBS Lett. 1999 Oct 29;460(2):207-11. Update 2003/08/25. // Entry E0645 Definition [Tropheryma whipplei.] Pyridoxal phosphate [cpd:C00018] (ET=CD); Pyridoxine [cpd:C00314] (ET=VD); Vitamin B6 metabolism [KEGG:map00750] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Threonine dehydratase (TdcB) [EC:4.3.1.19] uses pyridoxal phosphate as a cofactor [1,2]. There is no metabolic pathway for vitamin B6, including pyridoxal phosphate (according to KEGG [3]). Pyridoxine (vitamin form) and pyridoxal phosphate are generally involved in transamination, deamination, decarboxylation and racemation of amino acids. Hypothesis IN=cpd:C00018, Pyridoxal phosphate, ET=CD; IN=cpd:C00314, Pyridoxine, ET=VD. Gene TWT681; TW700. Pathway KEGG:map00750 Vitamin B6 metabolism. Reference [1] PubMed:9562556 Gallagher DT, Gilliland GL, Xiao G, Zondlo J, Fisher KE, Chinchilla D, Eisenstein E. "Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase." Structure. 1998 Apr 15;6(4):465-75. ; [2] PubMed:8112347 Alexander FW, Sandmeier E, Mehta PK, Christen P. "Evolutionary relationships among pyridoxal-5'-phosphate-dependent enzymes. Regio-specific alpha, beta and gamma families." Eur J Biochem. 1994 Feb 1;219(3):953-60. ; [3] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0646 Definition [Tropheryma whipplei.] Thiamin [cpd:C00378] (ET=VD); Thiamin diphosphate [cpd:C00068] (ET=CD); Thiamine metabolism [KEGG:map00730] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Acetolactate synthase [EC:2.2.1.6] requires thiamin diphosphate according to a metabolism check system (under development, H. Ogata). Tropheryma appears to lack the thiamin biosynthetis pathway (according to KEGG [1]). Hypothesis IN=cpd:C00378, Thiamin, ET=VD; IN=cpd:C00068, Thiamin diphosphate, ET=CD. Gene TWT205, TWT206; TW566, TW567. Pathway KEGG:map00730 Thiamine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/25. // Entry E0647 Definition [Tropheryma whipplei.] NH3 [cpd:C00014] (ET=S); Nitrogen metabolism [KEGG:twh00910] Organism Tropheryma whipplei (TAX:2039 Bacteria; Actinobacteria; Actinobacteria (class); Actinobacteridae; Actinomycetales; Micrococcineae; Cellulomonadaceae; Tropheryma). Evidence Nitrite and nitrate cannot be the source of nitrogen, but ammonia can be utilized (according to KEGG [1]). Hypothesis IN=cpd:C00014, NH3, ET=S. Gene Pathway KEGG:twh00910 Nitrogen metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // # # Evidence-Hypothesis Database for Coxiella burnetii # Entry E0801 Definition [Coxiella burnetii.] Amino acid [cpd:C00045] (ET=DGT); Peptide [cpd:C00012] (ET=TS); Oligopeptide [cpd:C00098] (ET=TS) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for amino acid and oligopeptide (TransportDB [1]). Amino acids appears to be dominant carbon sources for C. burnetii, and C. burnetii was predicted to be auxotroph for 11 amino acids [2]. The bacterium possesses about 20 peptidases. Hypothesis IN=cpd:C00045, Amino acid, ET=DGT; IN=cpd:C00012, Peptide, ET=TS; IN=cpd:C00098, Oligopeptide, ET=TS. Gene CBU0728, CBU0727, CBU0729; CBU0107, CBU0108, CBU0109; CBU1857, CBU1859, CBU1858, CBU1860; CBU1347; CBU0426; CBU2020; CBU1130. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:12704232 Seshadri R, Paulsen IT, Eisen JA, Read TD, Nelson KE, Nelson WC, Ward NL, Tettelin H, Davidsen TM, Beanan MJ, Deboy RT, Daugherty SC, Brinkac LM, Madupu R, Dodson RJ, Khouri HM, Lee KH, Carty HA, Scanlan D, Heinzen RA, Thompson HA, Samuel JE, Fraser CM, Heidelberg JF. "Complete genome sequence of the Q-fever pathogen Coxiella burnetii." Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5455-60. Epub 2003 Apr 18. Update 2003/08/19. // Entry E0802 Definition [Coxiella burnetii.] L-Arginine [cpd:C00062] (ET=GT) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for arginine (TransportDB [1]). Hypothesis IN=cpd:C00062, L-Arginine, ET=GT. Gene CBU0481, CBU0484, CBU0483, CBU0482. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0803 Definition [Coxiella burnetii.] Glycine [cpd:C00037] (ET=GT); Betaine [cpd:C00719] (ET=T); Carnitine [cpd:C00487] (ET=T); Choline [cpd:C00114] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for glycine, betaine, carnitine, choline (TransportDB [1]). Hypothesis IN=cpd:C00037, Glycine, ET=GT; IN=cpd:C00719, Betaine, ET=T; IN=cpd:C00487, Carnitine, ET=T; IN=cpd:C00114, Choline, ET=T. Gene CBU0178, CBU0177. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0804 Definition [Coxiella burnetii.] Nitrite [cpd:C00088] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for nitrite (TransportDB [1]). Hypothesis IN=cpd:C00088, Nitrite, ET=T. Gene CBU1770, CBU1771. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0805 Definition [Coxiella burnetii.] L-Arginine [cpd:C00062] (ET=TG); L-Lysine [cpd:C00047] (ET=TG) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for cationic amino acids (TransportDB [1]). Hypothesis IN=cpd:C00062, L-Arginine, ET=TG; IN=cpd:C00047, L-Lysine, ET=TG. Gene CBU0953; CBU1798. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0806 Definition [Coxiella burnetii.] L-Asparagine [cpd:C00152] (ET=GT) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for asparagine (TransportDB [1]). Hypothesis IN=cpd:C00152, L-Asparagine, ET=GT. Gene CBU0570; CBU1796. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0807 Definition [Coxiella burnetii.] Glycine [cpd:C00037] (ET=GT); Betaine [cpd:C00719] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for glycine, betaine (TransportDB [1]). Hypothesis IN=cpd:C00037, Glycine, ET=GT; IN=cpd:C00719, Betaine, ET=T. Gene CBU1646. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0808 Definition [Coxiella burnetii.] Sodium [cpd:C01330] (ET=T); Calcium [cpd:C00076] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for sodium/calcium (TransportDB [1]). Hypothesis IN=cpd:C01330, Sodium, ET=T; IN=cpd:C00076, Calcium, ET=T. Gene CBU0095. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0809 Definition [Coxiella burnetii.] Sodium [cpd:C01330] (ET=NT); H+ [cpd:C00080] (ET=NT); (pH=4.5) (ET=U) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for sodium/proton (TransportDB [1]). These sodium ion/proton exchangers probably play an important role in pH homeostasis and survival within the acidic phagolysosome (pH=4.5) [2]. Hypothesis IN=cpd:C01330, Sodium, ET=NT; IN=cpd:C00080, H+, ET=NT; IN=(pH=4.5), ET=U. Gene CBU1590; CBU1259; CBU0459; CBU1588, CBU1587, CBU1586, CBU1585, CBU1584, CBU1583, CBU1582. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100.; [2] PubMed:12704232 Seshadri R, Paulsen IT, Eisen JA, Read TD, Nelson KE, Nelson WC, Ward NL, Tettelin H, Davidsen TM, Beanan MJ, Deboy RT, Daugherty SC, Brinkac LM, Madupu R, Dodson RJ, Khouri HM, Lee KH, Carty HA, Scanlan D, Heinzen RA, Thompson HA, Samuel JE, Fraser CM, Heidelberg JF. "Complete genome sequence of the Q-fever pathogen Coxiella burnetii." Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5455-60. Epub 2003 Apr 18. Update 2003/08/19. // Entry E0810 Definition [Coxiella burnetii.] Sodium [cpd:C01330] (ET=NT); Sulfate [cpd:C00059] (ET=NT) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for sodium/sulfate (TransportDB [1]). Hypothesis IN=cpd:C01330, Sodium, ET=NT; IN=cpd:C00059, Sulfate, ET=NT. Gene CBU1066. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0811 Definition [Coxiella burnetii.] L-Tyrosine [cpd:C00082] (ET=GT) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for tyrosine (TransportDB [1]). Hypothesis IN=cpd:C00082, L-Tyrosine, ET=GT. Gene CBU1539. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0812 Definition [Coxiella burnetii.] Sugar [cpd:C11477] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for sugar (TransportDB [1]). Hypothesis IN=cpd:C11477, Sugar, ET=T. Gene CBU1484; CBU0906. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0813 Definition [Coxiella burnetii.] Hexose 1-phosphate [cpd:C01002] (ET=T); D-Hexose 6-phosphate [cpd:C02965] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for hexose phosphate (TransportDB [1]). Hypothesis IN=cpd:C01002, Hexose 1-phosphate, ET=T; IN=cpd:C02965, D-Hexose 6-phosphate, ET=T. Gene CBU0922; CBU0566. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0814 Definition [Coxiella burnetii.] Orthophosphate [cpd:C00009] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for phosphate (TransportDB [1]). Hypothesis IN=cpd:C00009, Orthophosphate, ET=T. Gene CBU0713; CBU0364; CBU0014. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0815 Definition [Coxiella burnetii.] D-Xylose [cpd:C00181] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for D-xylose (TransportDB [1]). Hypothesis IN=cpd:C00181, D-Xylose, ET=T. Gene CBU0347. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0816 Definition [Coxiella burnetii.] D-Glucose [cpd:C00031] (ET=T); D-Galactose [cpd:C00124] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for glucose/galactose (TransportDB [1]). Hypothesis IN=cpd:C00031, D-Glucose, ET=T; IN=cpd:C00124, D-Galactose, ET=T. Gene CBU0265. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0817 Definition [Coxiella burnetii.] L-Proline [cpd:C00148] (ET=GT); Betaine [cpd:C00719] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for proline/betaine (TransportDB [1]). Hypothesis IN=cpd:C00148, L-Proline, ET=GT; IN=cpd:C00719, Betaine, ET=T. Gene CBU2058. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0818 Definition [Coxiella burnetii.] Sodium [cpd:C01330] (ET=NT); Chloride [cpd:C00115] (ET=NT) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for sodium/chloride (TransportDB [1]). (Chloride may not have to be added). Hypothesis IN=cpd:C01330, Sodium, ET=NT; IN=cpd:C00115, Chloride, ET=NT. Gene CBU2088. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0819 Definition [Coxiella burnetii.] H+ [cpd:C00080] (ET=NT); Peptide [cpd:C00012] (ET=T) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for proton/peptide (TransportDB [1]). Hypothesis IN=cpd:C00080, H+, ET=NT; IN=cpd:C00012, Peptide, ET=T. Gene CBU0504; CBU0539. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0820 Definition [Coxiella burnetii.] Zinc [cpd:C00038] (ET=NTC) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for zinc ion (TransportDB [1]). Porphobilinogen synthase (HemB) [EC:4.2.1.24] uses zinc as a cofactor. Hypothesis IN=cpd:C00038, Zinc, ET=NTC. Gene CBU1511; CBU1424. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/25. // Entry E0821 Definition [Coxiella burnetii.] Iron [cpd:C00023] (ET=NT) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Presence of transporters for ferrous iron (Fe2+) (TransportDB [1]). Hypothesis IN=cpd:C00023, Iron, ET=NT. Gene CBU1766. Pathway Reference [1] PubMed:10926494 Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. "Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes." J Mol Biol. 2000 Aug 4;301(1):75-100. Update 2003/08/19. // Entry E0822 Definition [Coxiella burnetii.] Guanosine [cpd:C00387] (ET=T); Adenosine [cpd:C00212] (ET=T); Inosine [cpd:C00294] (ET=T); Thymidine [cpd:C00214] (ET=T); Uridine [cpd:C00299] (ET=T); (T=36C) (ET=E); embryonated chick egg (ET=E); (pH=4.0-5.5) (ET=E) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence C. burnetii uptake guanosine, adenosine, and inosine [1]. It also exhibit limited uptake of thymidine and uridine. It was not capable of transport and incorporation of NTPs, CMP, cytosine or uracil. Culture in this experiment [1] is in embryonated chicken eggs at 36 degree C, (at pH=4.0-5.5 typical of lysosomes). Hypothesis IN=cpd:C00387, Guanosine, ET=T; IN=cpd:C00212, Adenosine, ET=T; IN=cpd:C00294, Inosine, ET=T; IN=cpd:C00214, Thymidine, ET=T; IN=cpd:C00299, Uridine, ET=T; IN=(T=36C), ET=E; IN=embryonated chick egg, ET=E; IN=(pH=4.0-5.5), ET=E. Gene Pathway Reference [1] PubMed:12177333 Miller JD, Thompson HA. "Permeability of Coxiella burnetii to ribonucleosides." Microbiology. 2002 Aug;148(Pt 8):2393-403. Update 2003/08/19. // Entry E0823 Definition [Coxiella burnetii.] (pH=3.0-4.5) (ET=E); L-Proline [cpd:C00148] (ET=GT) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence L-proline transport is optimal at pH 3.0 to 4.5, the same pH range for the host phagolysosome. Hypothesis IN=(pH=3.0-4.5), ET=E; IN=cpd:C00148, L-Proline, ET=GT. Gene Pathway Reference [1] PubMed:6549343 Hendrix L, Mallavia LP. "Active transport of proline by Coxiella burnetii." J Gen Microbiol. 1984 Nov;130 ( Pt 11):2857-63. Update 2003/08/19. // Entry E0824 Definition [Coxiella burnetii.] (pH=3.5) (ET=E); L-Glutamate [cpd:C00025] (ET=TG) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence L-glutamate transport is pH dependent [1] (Vmax of 8.33 pmol/s per mg at pH 3.5). This transport can be inhibited by L-glutamine and L-asparagine. Hypothesis IN=(pH=3.5), ET=E; IN=cpd:C00025, L-Glutamate, ET=TG. Gene Pathway Reference [1] PubMed:6132912 Hackstadt T, Williams JC. "pH dependence of the Coxiella burnetii glutamate transport system." J Bacteriol. 1983 May;154(2):598-603. Update 2003/08/19. // Entry E0831 Definition [Coxiella burnetii.] polyketide (ET=D) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Several polyketide synthesis genes are present, but many of them are pseudogenes [1]. Hypothesis IN=polyketide, ET=D. Gene Pathway Reference [1] PubMed:12704232 Seshadri R, Paulsen IT, Eisen JA, Read TD, Nelson KE, Nelson WC, Ward NL, Tettelin H, Davidsen TM, Beanan MJ, Deboy RT, Daugherty SC, Brinkac LM, Madupu R, Dodson RJ, Khouri HM, Lee KH, Carty HA, Scanlan D, Heinzen RA, Thompson HA, Samuel JE, Fraser CM, Heidelberg JF. "Complete genome sequence of the Q-fever pathogen Coxiella burnetii." Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5455-60. Epub 2003 Apr 18. Update 2003/08/19. // Entry E0832 Definition [Coxiella burnetii.] D-Glucose [cpd:C00031] (ET=S); D-Galactose [cpd:C00124] (ET=S); D-Xylose [cpd:C00181] (ET=S); Glycerol [cpd:C00116] (ET=S) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Genome analysis reveals pathways for the utilization of few sugars including glucose, galactose, xylose and glycerol, although no transporter for glycerol has been identified [1]. Hypothesis IN=cpd:C00031, D-Glucose, ET=S; IN=cpd:C00124, D-Galactose, ET=S; IN=cpd:C00181, D-Xylose, ET=S; IN=cpd:C00116, Glycerol, ET=S. Gene Pathway Reference [1] PubMed:12704232 Seshadri R, Paulsen IT, Eisen JA, Read TD, Nelson KE, Nelson WC, Ward NL, Tettelin H, Davidsen TM, Beanan MJ, Deboy RT, Daugherty SC, Brinkac LM, Madupu R, Dodson RJ, Khouri HM, Lee KH, Carty HA, Scanlan D, Heinzen RA, Thompson HA, Samuel JE, Fraser CM, Heidelberg JF. "Complete genome sequence of the Q-fever pathogen Coxiella burnetii." Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5455-60. Epub 2003 Apr 18. Update 2003/08/19. // Entry E0833 Definition [Coxiella burnetii.] L-Tryptophan [cpd:C00078] (ET=DG); L-Lysine [cpd:C00047] (ET=DG); Indole [cpd:C00463] (ET=U) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Genome analysis indicates that tryptophan and lysine cannot be synthesized [1]. The pathway for lysine lacks the last step as in Rickettsia and Chlamydia, thus considered a diaminopimelate synthetic pathway [1]. Intermediates for tryptophan (for example, indole) may be also utilized [1,2]. Hypothesis IN=cpd:C00078, L-Tryptophan, ET=DG; IN=cpd:C00047, L-Lysine, ET=DG; IN=cpd:C00463, Indole, ET=U. Gene Pathway Reference [1] PubMed:12704232 Seshadri R, Paulsen IT, Eisen JA, Read TD, Nelson KE, Nelson WC, Ward NL, Tettelin H, Davidsen TM, Beanan MJ, Deboy RT, Daugherty SC, Brinkac LM, Madupu R, Dodson RJ, Khouri HM, Lee KH, Carty HA, Scanlan D, Heinzen RA, Thompson HA, Samuel JE, Fraser CM, Heidelberg JF. "Complete genome sequence of the Q-fever pathogen Coxiella burnetii." Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5455-60. Epub 2003 Apr 18.; [2] PubMed:12011099 Fehlner-Gardiner C, Roshick C, Carlson JH, Hughes S, Belland RJ, Caldwell HD, McClarty G. "Molecular basis defining human Chlamydia trachomatis tissue tropism. A possible role for tryptophan synthase." J Biol Chem. 2002 Jul 26;277(30):26893-903. Epub 2002 May 13. Update 2003/08/19. // Entry E0834 Definition [Coxiella burnetii.] NH3 [cpd:C00014] (ET=S); Nitrogen metabolism [KEGG:cbu00910] Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence C. burnetii may not use nitrate or nitrite as nitrogen sources. Ammonia could be a source of nitrogen (according to KEGG [1]). Hypothesis IN=cpd:C00014, NH3, ET=S. Gene Pathway KEGG:cbu00910 Nitrogen metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0835 Definition [Coxiella burnetii.] Thiamin [cpd:C00378] (ET=VD); Thiamin diphosphate [cpd:C00068] (ET=CD); Thiamine metabolism [KEGG:cbu00730] Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Thiamin (vitamin B1) biosynthetic pathway lacks the first part (according to KEGG [1]). A metabolism check system (under development, H. Ogata) suggests that C. burnetii requires thiamin diphosphate as a cofactor of enzymes. Hypothesis IN=cpd:C00378, Thiamin, ET=VD; IN=cpd:C00068, Thiamin diphosphate, ET=CD. Gene Pathway KEGG:cbu00730 Thiamine metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0837 Definition [Coxiella burnetii.] Nicotinate [cpd:C00253] (ET=VD); Nicotinate and nicotinamide metabolism [KEGG:cbu00760] Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence The biosynthetic pathway for NAD+ and NADP+ starts from nicotinate (according to KEGG [1]). A metabolism check system (under development, H. Ogata) suggests that C. burnetii requires NAD+ as a cofactor of enzymes. Hypothesis IN=cpd:C00253, Nicotinate, ET=VD. Gene Pathway KEGG:cbu00760 Nicotinate and nicotinamide metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0838 Definition [Coxiella burnetii.] (R)-Pantoate [cpd:C00522] (ET=VD); Pantothenate and CoA biosynthesis [KEGG:cbu00770] Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence The biosynthetic pathway for coenzyme A (CoA) could start from pantoate (according to KEGG [1]). Hypothesis IN=cpd:C00522, (R)-Pantoate, ET=VD. Gene Pathway KEGG:cbu00770 Pantothenate and CoA biosynthesis. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0839 Definition [Coxiella burnetii.] Protoporphyrin [cpd:C02191] (ET=D); Heme [cpd:C00032] (ET=D); Porphyrin and chlorophyll metabolism [KEGG:cbu00860] Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence The porphyrin biosynthesis pathway lacks HemYG [EC:1.3.3.4] (according to KEGG [1]). Hypothesis IN=cpd:C02191, Protoporphyrin, ET=D; IN=cpd:C00032, Heme, ET=D. Gene Pathway KEGG:cbu00860 Porphyrin and chlorophyll metabolism. Reference [1] PubMed:11752249 Kanehisa M, Goto S, Kawashima S, Nakaya A. "The KEGG databases at GenomeNet." Nucleic Acids Res. 2002 Jan 1;30(1):42-6. Update 2003/08/19. // Entry E0840 Definition [Coxiella burnetii.] Cobalt [cpd:C00175] (ET=NC); NAD+ [cpd:C00003] (ET=C) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence 3-dehydroquinate synthase (AroB) [EC:4.2.3.4] requires cobalt and NAD as cofactors. Hypothesis IN=cpd:C00175, Cobalt, ET=NC; IN=cpd:C00003, NAD+, ET=C. Gene CBU1893. Pathway Reference [1] PubMed:2514789 Bender SL, Mehdi S, Knowles JR. "Dehydroquinate synthase: the role of divalent metal cations and of nicotinamide adenine dinucleotide in catalysis." Biochemistry. 1989 Sep 19;28(19):7555-60. Update 2003/08/25. // Entry E0841 Definition [Coxiella burnetii.] Iron [cpd:C00023] (ET=NC); Copper [cpd:C00070] (ET=NC); Zinc [cpd:C00038] (ET=NC); Manganese [cpd:C00034] (ET=NC) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Superoxide dismutase [EC:1.15.1.1] uses iron or copper/zinc or manganese as a cofactor [1,2]. Hypothesis IN=cpd:C00023, Iron, ET=NC; IN=cpd:C00070, Copper, ET=NC; IN=cpd:C00038, Zinc, ET=NC; IN=cpd:C00034, Manganese, ET=NC. Gene CBU1708, CBU1822. Pathway Reference [1] PubMed:2669953 Beyer WF Jr, Reynolds JA, Fridovich I. "Differences between the manganese- and the iron-containing superoxide dismutases of Escherichia coli detected through sedimentation equilibrium, hydrodynamic, and spectroscopic studies." Biochemistry. 1989 May 16;28(10):4403-9. ; [2] PubMed:10419947 Santos R, Bocquet S, Puppo A, Touati D. "Characterization of an atypical superoxide dismutase from Sinorhizobium meliloti." J Bacteriol. 1999 Aug;181(15):4509-16. Update 2003/08/25. // Entry E0842 Definition [Coxiella burnetii.] Iron-sulfur [cpd:C00824] (ET=C) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Biotin synthase (BioB) [EC:2.8.1.6] uses iron-sulfur as a cofactor [1]. Hypothesis IN=cpd:C00824, Iron-sulfur, ET=C. Gene CBU1007. Pathway Reference [1] PubMed:12475249 Benda R, Tse Sum Bui B, Schunemann V, Florentin D, Marquet A, Trautwein AX. "Iron-sulfur clusters of biotin synthase in vivo: a Mossbauer study." Biochemistry. 2002 Dec 17;41(50):15000-6. Update 2003/08/25. // Entry E0843 Definition [Coxiella burnetii.] dipyrromethane (ET=C) Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Porphobilinogen deaminase (HemC) [EC:4.3.1.8] requires dipyrromethane as a cofactor [1-3]. Hypothesis IN=dipyrromethane, ET=C. Gene CBU2074. Pathway Reference [1] PubMed:9766005 McNeill LA, Shoolingin-Jordan PM. "Dipyrromethane cofactor assembly in porphobilinogen deaminase." Biochem Soc Trans. 1998 Aug;26(3):S286. No abstract available. ; [2] PubMed:8687374 Shoolingin-Jordan PM, Warren MJ, Awan SJ. "Discovery that the assembly of the dipyrromethane cofactor of porphobilinogen deaminase holoenzyme proceeds initially by the reaction of preuroporphyrinogen with the apoenzyme." Biochem J. 1996 Jun 1;316 ( Pt 2):373-6. ; [3] PubMed:1522882 Louie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Warren MJ, Woodcock SC, Jordan PM. "Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site." Nature. 1992 Sep 3;359(6390):33-9. Update 2003/08/25. // Entry E0844 Definition [Coxiella burnetii.] Magnesium [cpd:C00305] (ET=NT); Glycolysis / Gluconeogenesis [KEGG:cbu00010] Organism Coxiella burnetii (TAX:777 Bacteria; Proteobacteria; Gammaproteobacteria; Legionellales; Coxiellaceae; Coxiella). Evidence Enolase [EC:4.2.1.11] uses magnesium as a cofactor [1]. Hypothesis IN=cpd:C00305, Magnesium, ET=NT. Gene CBU1674. Pathway KEGG:cbu00010 Glycolysis / Gluconeogenesis. Reference [1] PubMed:8994873 Reed GH, Poyner RR, Larsen TM, Wedekind JE, Rayment I. "Structural and mechanistic studies of enolase." Curr Opin Struct Biol. 1996 Dec;6(6):736-43. Review. Update 2003/08/25. //