Metagrowth: a database of evidences and hypotheses for the study of culture conditions of obligate parasitic bacteria

Total number of physical conditions and nutriments: 56
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Hypothesis / Physical conditions or nutriments Evidence type Evidences / Rickettsia prowazekii and R. conorii
Pyruvate
C00022 		CDRS E0401 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.
Malate
C00711 		T E0411 Presence of transporters for malate (TransportDB [1]).
Glycerol 3-phosphate
C00093 		T E0417 Presence of transporters for glycerol-3-phosphate (TransportDB [1]).
Dicarboxylate
C02028 		T E0415 Presence of transporters for sodium/dicarboxylate (TransportDB [1]).
Amino acid
C00045 		DGT E0404 Presence of transporters for amino acid (TransportDB [1]).

E0425 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.
L-Arginine
C00062 		GT E0412 Presence of transporters for cationic amino acid (TransportDB [1]).

E0413 Presence of transporters for arginine/ornithine (TransportDB [1]).
L-Glutamine
C00064 		GT E0403 Presence of transporters for glutamine (TransportDB [1]).
L-Glutamate
C00025 		GT E0414 Presence of transporters for proton/glutamate (TransportDB [1]).
L-Isoleucine
C00407 		GT E0405 Presence of transporters for branched chain amino acid (TransportDB [1]).
L-Leucine
C00123 		GT E0405 Presence of transporters for branched chain amino acid (TransportDB [1]).
L-Lysine
C00047 		GT E0412 Presence of transporters for cationic amino acid (TransportDB [1]).
L-Proline
C00148 		GT E0418 Presence of transporters for proline (osmoprotection) (TransportDB [1]).

E0419 Presence of transporters for proline/betaine (TransportDB [1]).
L-Valine
C00183 		GT E0405 Presence of transporters for branched chain amino acid (TransportDB [1]).
L-Ornithine
C00077 		T E0413 Presence of transporters for arginine/ornithine (TransportDB [1]).
AMP
C00020 		DS E0423 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]).
dAMP
C00360 		DS E0423 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]).
ATP
C00002 		GT E0410 Presence of transporters for ATP/ADP (TransportDB [1] and [2,3]).
GMP
C00144 		DS E0423 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]).
dGMP
C00362 		DS E0423 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]).
Thymidine
C00214 		DS E0424 There is no biosynthetic pathway for pyrimidines. Minimal requirement for the salvage pathway appears thymidine (according to KEGG [1]).
Tetrahydrofolate
C00101 		DS E0432 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.
Folic acid
C00504 		DS E0432 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.
Biotin
C00120 		CD E0431 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].
NAD+
C00003 		DS E0429 No biosynthetic pathway for NAD+, which enters into the TCA cycle (according to KEGG [1]).
CoA
C00010 		DS E0430 No biosynthetic pathway for coenzyme A (CoA) (according to KEGG [1]), which is required for TCA cycle of Rickettsia.
Malonyl-CoA
C00083 		DS E0422 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.
Pantothenate
C00864 		T E0421 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.)
Pyridoxal phosphate
C00018 		CD E0441 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.
Pyridoxine
C00314 		DV E0441 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.
FAD
C00016 		CD E0437 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]).
Riboflavin-5-phosphate
C00061 		CD E0437 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]).
Thiamin diphosphate
C00068 		CD E0442 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]).
Thiamin (vitamin B1)
C00378 		DV E0442 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]).
Heme
C00032 		CDT E0406 Presence of transporters for heme (TransportDB [1]).

E0433 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.

E0438 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]).
Protoporphyrin
C02191 		D E0433 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.
Ubiquinone (Coenzyme Q)
C00399 		D E0434 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.
S-Adenosyl-L-methionine
C00019 		DT E0435 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.
dipyrromethane C E0439 Porphobilinogen deaminase (HemC) [EC:4.3.1.8] requires dipyrromethane as a cofactor [1-3].
Glutathione
C00051 		DS E0427 Rickettsia appear to lack the biosynthetic pathway for glutathione (according to KEGG [1]). However glutathione S-transferase [EC:2.5.1.18] is present.
Chorismate
C00251 		DS E0434 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.
D-Glutamate
C00217 		DS E0426 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]).
Betaine
C00719 		T E0419 Presence of transporters for proline/betaine (TransportDB [1]).
Iron-sulfur
C00824 		CN E0440 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].
Phosphatidate
C00416 		DS E0428 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].
1-Acyl-sn-glycerol 3-phosphate
C00681 		U E0428 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].
Iron (Fe2+,Fe3+)
C00023 		CN E0440 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].
Zinc (Zn2+)
C00038 		CNT E0402 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].

E0438 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]).
Copper (Cu2+)
C00070 		CN E0438 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]).
Manganese (Mn2+)
C00034 		CNT E0402 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].

E0437 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]).
Cobalt (Co2+)
C00175 		T E0409 Presence of transporters for magnesium/cobalt (TransportDB [1]).
NH3
C00014 		U E0436 Rickettsia may have two-component system for nitrogen assimilation (NtrX/NtrY) (according to KEGG [1]).
Calcium (Ca2+)
C00076 		CN E0437 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]).
H+
C00080 		T E0407 Presence of transporters for proton, ATP synthase (TransportDB [1]).

E0414 Presence of transporters for proton/glutamate (TransportDB [1]).

E0420 Presence of transporters for sodium/proton (TransportDB [1]).
Magnesium (Mg2+)
C00305 		CNT E0409 Presence of transporters for magnesium/cobalt (TransportDB [1]).

E0437 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]).

E0438 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]).
Sodium (Na+)
C01330 		CNT E0415 Presence of transporters for sodium/dicarboxylate (TransportDB [1]).

E0420 Presence of transporters for sodium/proton (TransportDB [1]).

E0421 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.)

E0438 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]).
Fatty acid
C00162 		DG E0422 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.