Accepted name: citrate (Si)-synthase
Reaction: acetyl-CoA + H2O + oxaloacetate = citrate + CoA
For diagram of reaction click here or click here.
Other name(s): (R)-citric synthase; citrate oxaloacetate-lyase [(pro-3S)-CH2COO-→acetyl-CoA]
Systematic name: acetyl-CoA:oxaloacetate C-acetyltransferase [thioester-hydrolysing, (pro-S)-carboxymethyl forming]
Comments: The stereospecificity of this enzyme is opposite to that of EC 2.3.3.3, citrate (Re)-synthase, which is found in some anaerobes. Citrate synthase for which the stereospecificity with respect to C-2 of oxaloacetate has not been established are included in EC 2.3.3.16, citrate synthase.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9027-96-7
References:
1. Lenz, H., Buckel, W., Wunderwald, P., Biedermann, G., Buschmeier, V., Eggerer, H., Cornforth, J.W., Redmond, J.W. and Mallaby, R. Stereochemistry of si-citrate synthase and ATP-citrate-lyase reactions. Eur. J. Biochem. 24 (1971) 207-215. [PMID: 5157292]
2. Karpusas, M., Branchaud, B. and Remington, S.J. Proposed mechanism for the condensation reaction of citrate synthase: 1.9-Å structure of the ternary complex with oxaloacetate and carboxymethyl coenzyme A. Biochemistry 29 (1990) 2213-2219. [PMID: 2337600]
3. van Rooyen, J.P., Mienie, L.J., Erasmus, E., De Wet, W.J., Ketting, D., Duran, M. and Wadman, S.K. Identification of the stereoisomeric configurations of methylcitric acid produced by si-citrate synthase and methylcitrate synthase using capillary gas chromatography-mass spectrometry. J. Inherit. Metab. Dis. 17 (1994) 738-747. [PMID: 7707698]
Accepted name: decylcitrate synthase
Reaction: lauroyl-CoA + H2O + oxaloacetate = (2S,3S)-2-hydroxytridecane-1,2,3-tricarboxylate + CoA
For diagram click here.
Other name(s): 2-decylcitrate synthase; (2S,3S)-2-hydroxytridecane-1,2,3-tricarboxylate oxaloacetate-lyase (CoA-acylating)
Systematic name: dodecanoyl-CoA:oxaloacetate C-dodecanoyltransferase (thioester-hydrolysing, 1-carboxyundecyl-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9068-72-8
References:
1. Måhlén, A. and Gatenbeck, S. A metabolic variation in Penicillium spiculisporum Lehman. II. Purification and some properties of the enzyme synthesizing (–)-decylcitric acid. Acta Chem. Scand. 22 (1968) 2617-2623. [PMID: 5719165]
2. Måhlén, A. Properties of 2-decylcitrate synthase from Penicillium spiculisporum Lehman. Eur. J. Biochem. 22 (1971) 104-114. [PMID: 5099208]
Accepted name: citrate (Re)-synthase
Reaction: acetyl-CoA + H2O + oxaloacetate = citrate + CoA
For diagram click here.
Other name(s): (R)-citrate synthase; Re-citrate-synthase; citrate oxaloacetate-lyase [(pro-3R)-CH2COO-→acetyl-CoA]
Systematic name: acetyl-CoA:oxaloacetate C-acetyltransferase [thioester-hydrolysing, (pro-R)-carboxymethyl-forming]
Comments: This enzyme is inactivated by oxygen and is found in some anaerobes. Its stereospecificity is opposite to that of EC 2.3.3.1, citrate (Si)-synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9077-70-7
References:
1. Dittbrenner, S., Chowdhury, A.A. and Gottschalk, G. The stereospecificity of the (R)-citrates synthase in the presence of p-chloromercuribenzoate. Biochem. Biophys. Res. Commun. 36 (1969) 802-808. [PMID: 5808294]
2. Gottschalk, G. Partial purification and some properties of the (R)-citrate synthase from Clostridium acidi-urici. Eur. J. Biochem. 7 (1969) 301-306. [PMID: 4974734]
3. Gottschalk, G. and Barker, H.A. Synthesis of glutamate and citrate by Clostridium kluyveri. A new type of citrate synthase. Biochemistry 5 (1966) 1125-1133. [PMID: 5958189]
Accepted name: decylhomocitrate synthase
Reaction: dodecanoyl-CoA + H2O + 2-oxoglutarate = (3S,4S)-3-hydroxytetradecane-1,3,4-tricarboxylate + CoA
For diagram click here.
Other name(s): 2-decylhomocitrate synthase; 3-hydroxytetradecane-1,3,4-tricarboxylate 2-oxoglutarate-lyase (CoA-acylating)
Systematic name: dodecanoyl-CoA:2-oxoglutarate C-dodecanoyltransferase (thioester-hydrolysing, 1-carboxyundecyl-forming)
Comments: Decanoyl-CoA can act instead of dodecanoyl-CoA, but 2-oxoglutarate cannot be replaced by oxaloacetate or pyruvate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 51845-40-0
References:
1. Måhlén, A. Purification and some properties of 2-decylhomocitrate synthase from Penicillium spiculisporum. Eur. J. Biochem. 38 (1973) 32-39. [PMID: 4774124]
2. Brandäge, S., Dahlman, O., Lindqvist, B., Måhlén, A. and Mörch, L. Absolute configuration and enantiospecific synthesis of spiculisporic acid. Acta Chem. Scand. 38B (1984) 837-844.
Accepted name: 2-methylcitrate synthase
Reaction: propanoyl-CoA + H2O + oxaloacetate = (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate + CoA
For diagram of reaction click here.
Glossary: 2-methylcitrate = (2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate
Other name(s): 2-methylcitrate oxaloacetate-lyase; MCS; methylcitrate synthase; methylcitrate synthetase
Systematic name: propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming)
Comments: The enzyme acts on acetyl-CoA, propanoyl-CoA, butanoyl-CoA and pentanoyl-CoA. The relative rate of condensation of acetyl-CoA and oxaloacetate is 140% of that of propanoyl-CoA and oxaloacetate, but the enzyme is distinct from EC 2.3.3.1, citrate (Si)-synthase. Oxaloacetate cannot be replaced by glyoxylate, pyruvate or 2-oxoglutarate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 57827-78-8
References:
1. Uchiyama, H. and Tabuchi, T. Properties of methylcitrate synthase from Candida lipolytica. Agric. Biol. Chem. 40 (1976) 1411-1418.
2. Textor, S., Wendisch, V.F., De Graaf, A.A., Muller, U., Linder, M.I., Linder, D. and Buckel, W. Propionate oxidation in Escherichia coli: evidence for operation of a methylcitrate cycle in bacteria. Arch. Microbiol. 168 (1997) 428-436. [PMID: 9325432]
3. Horswill, A.R. and Escalante-Semerena, J.C. Salmonella typhimurium LT2 catabolizes propionate via the 2-methylcitric acid cycle. J. Bacteriol. 181 (1999) 5615-5623. [PMID: 10482501]
4. Brock, M., Maerker, C., Schütz, A., Völker, U. and Buckel, W. Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase. Eur. J. Biochem. 269 (2002) 6184-6194. [PMID: 12473114]
5. Domin, N., Wilson, D. and Brock, M. Methylcitrate cycle activation during adaptation of Fusarium solani and Fusarium verticillioides to propionyl-CoA-generating carbon sources. Microbiology 155 (2009) 3903-3912. [PMID: 19661181]
Accepted name: 2-ethylmalate synthase
Reaction: acetyl-CoA + H2O + 2-oxobutanoate = (R)-2-ethylmalate + CoA
For diagram click here.
Other name(s): (R)-2-ethylmalate 2-oxobutanoyl-lyase (CoA-acetylating); 2-ethylmalate-3-hydroxybutanedioate synthase; propylmalate synthase; propylmalic synthase
Systematic name: acetyl-CoA:2-oxobutanoate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
Comments: Also acts on (R)-2-(n-propyl)-malate. Formerly wrongly included with EC 2.3.3.7 3-ethylmalate synthase.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9024-01-5
References:
1. Strassman, M. and Ceci, L.N. A study of acetyl-CoA condensation with α-keto acids. Arch. Biochem. Biophys. 119 (1967) 420-428. [PMID: 6052435]
Accepted name: 3-ethylmalate synthase
Reaction: butanoyl-CoA + H2O + glyoxylate = 3-ethylmalate + CoA
For diagram click here.
Other name(s): 2-ethyl-3-hydroxybutanedioate synthase; 3-ethylmalate glyoxylate-lyase (CoA-butanoylating)
Systematic name: butanoyl-CoA:glyoxylate C-butanoyltransferase (thioester-hydrolysing, 1-carboxypropyl-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9024-01-5
References:
1. Ramasarma, T. and Giri, K.V. Phosphoglucose isomerase of green gram (Phaseolus radiatus). Arch. Biochem. Biophys. 62 (1956) 91-96.
Accepted name: ATP citrate synthase
Reaction: ADP + phosphate + acetyl-CoA + oxaloacetate = ATP + citrate + CoA
Other name(s): ATP-citric lyase; ATP:citrate oxaloacetate-lyase [(pro-S)-CH2COO-→acetyl-CoA] (ATP-dephosphorylating); acetyl-CoA:oxaloacetate acetyltransferase (isomerizing; ADP-phosphorylating); adenosine triphosphate citrate lyase; citrate cleavage enzyme; citrate-ATP lyase; citric cleavage enzyme; ATP citrate (pro-S)-lyase
Systematic name: acetyl-CoA:oxaloacetate C-acetyltransferase [(pro-S)-carboxymethyl-forming, ADP-phosphorylating]
Comments: The enzyme can be dissociated into components, two of which are identical with EC 4.1.3.34 (citryl-CoA lyase) and EC 6.2.1.18 (citrate—CoA ligase).
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9027-95-6
References:
1. Lill, U., Schreil, A. and Eggerer, H. Isolation of enzymically active fragments formed by limited proteolysis of ATP citrate lyase. Eur. J. Biochem. 125 (1982) 645-650. [PMID: 6749502]
2. Srere, P.A. and Lipmann, F. An enzymatic reaction between citrate, adenosine triphosphate and coenzyme A. J. Am. Chem. Soc. 75 (1953) 4874 only.
Accepted name: malate synthase
Reaction: acetyl-CoA + H2O + glyoxylate = (S)-malate + CoA
For diagram of reaction click here.
Other name(s): L-malate glyoxylate-lyase (CoA-acetylating); glyoxylate transacetylase; glyoxylate transacetase; glyoxylic transacetase; malate condensing enzyme; malate synthetase; malic synthetase; malic-condensing enzyme; acetyl-CoA:glyoxylate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
Systematic name: acetyl-CoA:glyoxylate C-acetyltransferase [(S)-malate-forming]
Comments: The enzyme catalyses the irreversible condensation of acetyl-CoA with glyoxylate to form (S)-malate. Among other functions, the enzyme participates in the glyoxylate cycle, a modified version of the TCA cycle that bypasses steps that lead to a loss of CO2.
Links to other databases: BRENDA, EXPASY, GTD, KEGG, Metacyc, PDB, CAS registry number: 9013-48-3
References:
1. Dixon, G.H., Kornberg, H.L. and Lund, P. Purification and properties of malate synthetase. Biochim. Biophys. Acta 41 (1960) 217-233. [PMID: 13816984]
Accepted name: hydroxymethylglutaryl-CoA synthase
Reaction: acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA
For diagram click here.
Other name(s): (S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating); 3-hydroxy-3-methylglutaryl CoA synthetase; 3-hydroxy-3-methylglutaryl coenzyme A synthase; 3-hydroxy-3-methylglutaryl coenzyme A synthetase; 3-hydroxy-3-methylglutaryl-CoA synthase; 3-hydroxy-3-methylglutaryl-coenzyme A synthase; β-hydroxy-β-methylglutaryl-CoA synthase; HMG-CoA synthase; acetoacetyl coenzyme A transacetase; hydroxymethylglutaryl coenzyme A synthase; hydroxymethylglutaryl coenzyme A-condensing enzyme
Systematic name: acetyl-CoA:acetoacetyl-CoA C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9027-44-5
References:
1. Rudney, H. The biosynthesis of β-hydroxy-β-methylglutaric acid. J. Biol. Chem. 227 (1957) 363-377.
Accepted name: 2-hydroxyglutarate synthase
Reaction: propanoyl-CoA + H2O + glyoxylate = 2-hydroxyglutarate + CoA
Other name(s): 2-hydroxyglutaratic synthetase; 2-hydroxyglutaric synthetase; α-hydroxyglutarate synthase; hydroxyglutarate synthase; 2-hydroxyglutarate glyoxylate-lyase (CoA-propanoylating)
Systematic name: propanoyl-CoA:glyoxylate C-propanoyltransferase (thioester-hydrolysing, 2-carboxyethyl-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 9024-02-6
References:
1. Reeves, H.C. and Ajl, S.J. α-Hydroxyglutaric acid synthetase. J. Bacteriol. 84 (1962) 186-187.
Accepted name: 3-propylmalate synthase
Reaction: pentanoyl-CoA + H2O + glyoxylate = 3-propylmalate + CoA
For diagram click here.
Other name(s): 3-(n-propyl)-malate synthase; 3-propylmalate glyoxylate-lyase (CoA-pentanoylating); β-n-propylmalate synthase; n-propylmalate synthase
Systematic name: pentanoyl-CoA:glyoxylate C-pentanoyltransferase (thioester-hydrolysing, 1-carboxybutyl-forming)
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 37290-62-3
References:
1. Imai, K., Reeves, H.C. and Ajl, S.J. n-Propylmalate synthetase. J. Biol. Chem. 238 (1963) 3193-3198.
Accepted name: 2-isopropylmalate synthase
Reaction: acetyl-CoA + 3-methyl-2-oxobutanoate + H2O = (2S)-2-isopropylmalate + CoA
For diagram of reaction click here.
Other name(s): 3-carboxy-3-hydroxy-4-methylpentanoate 3-methyl-2-oxobutanoate-lyase (CoA-acetylating); α-isopropylmalate synthetase; α-isopropylmalate synthase; α-isopropylmalic synthetase; isopropylmalate synthase; isopropylmalate synthetase
Systematic name: acetyl-CoA:3-methyl-2-oxobutanoate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
Comments: Requires K+.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9030-98-2
References:
1. Kohlhaw, G., Leary, T.R. and Umbarger, H.E. α-Isopropylmalate synthase from Salmonella typhimurium. Purification and properties. J. Biol. Chem. 244 (1969) 2218-2225. [PMID: 4976555]
2. Webster, R.E. and Gross, S.R. The α-isopropylmalate synthetase of Neurospora. I. The kinetics and end product control of α-isopropylmalate synthetase function. Biochemistry 4 (1965) 2309-2327.
3. Cole, F.E., Kalyanpur, M. G. and Stevens, C. M. Absolute configuration of α-isopropylmalate and the mechanism of its conversion to β-isopropylmalate in the biosynthesis of leucine. Biochemistry 12 (1973) 3346-3350. [PMID: 4270046]
Accepted name: homocitrate synthase
Reaction: acetyl-CoA + H2O + 2-oxoglutarate = (R)-2-hydroxybutane-1,2,4-tricarboxylate + CoA
For diagram click here, another example.
Glossary: (R)-homocitrate = (R)-2-hydroxybutane-1,2,4-tricarboxylate
Other name(s): 2-hydroxybutane-1,2,4-tricarboxylate 2-oxoglutarate-lyase (CoA-acetylating); acetyl-coenzyme A:2-ketoglutarate C-acetyl transferase; homocitrate synthetase; HCS
Systematic name: acetyl-CoA:2-oxoglutarate C-acetyltransferase (thioester-hydrolysing, carboxymethyl forming)
Comments: Belongs in the α-aminoadipate pathway of lysine synthesis, along with EC 4.2.1.36, homoaconitate hydratase. The enzyme also acts with oxaloacetate as substrate, but more slowly [2,3].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9075-60-9
References:
1. Strassman, M. and Ceci, L.N. Enzymatic formation of homocitric acid, an intermediate in lysine biosynthesis. Biochem. Biophys. Res. Commun. 14 (1964) 262-267. [PMID: 5836514]
2. Wulandari, A.P., Miyazaki, J., Kobashi, N., Nishiyama, M., Hoshino, T. and Yamane, H. Characterization of bacterial homocitrate synthase involved in lysine biosynthesis. FEBS Lett. 522 (2002) 35-40. [PMID: 12095615]
3. Andi, B., West, A.H. and Cook, P.F. Kinetic mechanism of histidine-tagged homocitrate synthase from Saccharomyces cerevisiae. Biochemistry 43 (2004) 11790-11795. [PMID: 15362863]
Accepted name: sulfoacetaldehyde acetyltransferase
Reaction: acetyl phosphate + sulfite = 2-sulfoacetaldehyde + phosphate
Glossary: 2-sulfoacetaldehyde = 2-oxoethanesulfonate
Other name(s): Xsc
Systematic name: acetyl-phosphate:sulfite S-acetyltransferase (acyl-phosphate hydrolysing, 2-oxoethyl-forming)
Comments: The reaction occurs in the reverse direction to that shown above. Requires Mg2+.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number: 56941-15-2
References:
1. Ruff, J, Denger, K. and Cook, A.M. Sulphoacetaldehyde acetyltransferase yields acetyl phosphate: purification from Alcaligenes defragrans and gene clusters in taurine degradation. Biochem. J. 369 (2003) 275-285. [PMID: 12358600]
Accepted name: citrate synthase (unknown stereospecificity)
Reaction: acetyl-CoA + H2O + oxaloacetate = citrate + CoA
Other name(s): citrate condensing enzyme; CoA-acetylating citrate oxaloacetate-lyase; citrate synthetase; citric synthase; citric-condensing enzyme; citrogenase; condensing enzyme (ambiguous); oxaloacetate transacetase; oxalacetic transacetase
Systematic name: acetyl-CoA:oxaloacetate C-acetyltransferase (thioester-hydrolysing)
Comments: This entry has been included to accommodate those citrate synthases for which the stereospecificity with respect to C-2 of oxaloacetate has not been established [cf. EC 2.3.3.1, citrate (Si)-synthase and EC 2.3.3.3, citrate (Re)-synthase].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Lohlein-Werhahn, G., Goepfert, P. and Eggerer, H. Purification and properties of an archaebacterial enzyme: citrate synthase from Sulfolobus solfataricus. Biol Chem Hoppe Seyler 369 (1988) 109-113. [PMID: 3130075]
2. Sievers, M., Stockli, M. and Teuber, M. Purification and properties of citrate synthase from Acetobacter europaeus. FEMS Microbiol. Lett. 146 (1997) 53-58. [PMID: 8997706]
3. Belova, L.L., Sokolov, A.P., Morgunov, I.G. and Trotsenko YuA. Purification and characterization of citrate synthase from Methylobacterium extorquens—a methylotrophic producer of polyhydroxybutyrate. Biochemistry (Mosc.) 62 (1997) 71-76. [PMID: 9113733]
4. Lee, S., Park, C. and Yim, J. Characterization of citrate synthase purified from Drosophila melanogaster. Mol. Cells 7 (1997) 599-604. [PMID: 9387145]
5. Maurus, R., Nguyen, N.T., Stokell, D.J., Ayed, A., Hultin, P.G., Duckworth, H.W. and Brayer, G.D. Insights into the evolution of allosteric properties. The NADH binding site of hexameric type II citrate synthases. Biochemistry 42 (2003) 5555-5565. [PMID: 12741811]
Accepted name: methylthioalkylmalate synthase
Reaction: an ω-(methylsulfanyl)-2-oxoalkanoate + acetyl-CoA + H2O = a 2-[ω-(methylsulfanyl)alkyl]malate + CoA
For diagram of reaction click here.
Other name(s): MAM1 (gene name); MAM3 (gene name); acetyl-CoA:ω-(methylthio)-2-oxoalkanoate C-acetyltransferase
Systematic name: acetyl-CoA:ω-(methylsulfanyl)-2-oxoalkanoate C-acetyltransferase
Comments: The enzyme, characterized from the plant Arabidopsis thaliana, is involved in the L-methionine side-chain elongation pathway, forming substrates for the biosynthesis of aliphatic glucosinolates. Two forms are known - MAM1 catalyses only only the first two rounds of methionine chain elongation, while MAM3 catalyses all six cycles, up to formation of L-hexahomomethionine.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, CAS registry number:
References:
1. Textor, S., Bartram, S., Kroymann, J., Falk, K.L., Hick, A., Pickett, J.A. and Gershenzon, J. Biosynthesis of methionine-derived glucosinolates in Arabidopsis thaliana: recombinant expression and characterization of methylthioalkylmalate synthase, the condensing enzyme of the chain-elongation cycle. Planta 218 (2004) 1026-1035. [PMID: 14740211]
2. Textor, S., de Kraker, J.W., Hause, B., Gershenzon, J. and Tokuhisa, J.G. MAM3 catalyzes the formation of all aliphatic glucosinolate chain lengths in Arabidopsis. Plant Physiol. 144 (2007) 60-71. [PMID: 17369439]
Accepted name: 2-phosphinomethylmalate synthase
Reaction: acetyl-CoA + H2O + 3-(hydroxyphosphinoyl)pyruvate = phosphinomethylmalate + CoA
Other name(s): pmmS (gene name)
Systematic name: acetyl-CoA:phosphinopyruvate C-acetyltransferase (thioester-hydrolysing, phosphinomethylmalate-forming)
Comments: The enzyme, characterized from the bacterium Streptomyces hygroscopicus, participates in the pathway for bialaphos biosynthesis. It requires a divalent metal ion and can also act on oxaloacetate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Shimotohno, K.W., Seto, H., Otake, N., Imai, S. and Murakami, T. Studies on the biosynthesis of bialaphos (SF-1293). 8. Purification and characterization of 2-phosphinomethylmalic acid synthase from Streptomyces hygroscopicus SF-1293. J. Antibiot. (Tokyo) 41 (1988) 1057-1065. [PMID: 3170341]
2. Shimotohno, K.W., Imai, S., Murakami, T. and Seto, H. Purification and characterization of citrate synthase from Streptomyces hygroscopicus SF-1293 and comparison of its properties with those of 2-phosphinomethylmalic acid synthase. Agric. Biol. Chem. 54 (1990) 463-470. [PMID: 1368511]
Accepted name: 2-phosphonomethylmalate synthase
Reaction: acetyl-CoA + H2O + 3-phosphonopyruvate = (R)-2-(phosphonomethyl)malate + CoA
Other name(s): 2-phosphinomethylmalic acid synthase; PMM synthase
Systematic name: acetyl-CoA:3-phosphonopyruvate C-acetyltransferase
Comments: The enzyme, isolated from several Streptomyces species, participate in the biosynthesis of certain phosphonate antibiotics. The enzyme is analogous to EC 2.3.3.1 (Si)-citrate synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Shimotohno, K., Seto, H., Otake, N., Imai, S. and Satoh, A. Studies on the biosynthesis of bialaphos (SE-1293). 7. The absolute configuration of 2-phosphinomethylmalic acid, a biosynthetic intermediate of bialaphos. J. Antibiot. (Tokyo) 39 (1986) 1356-1359. [PMID: 3781934]
2. Shimotohno, K.W., Seto, H., Otake, N., Imai, S. and Murakami, T. Studies on the biosynthesis of bialaphos (SF-1293). 8. Purification and characterization of 2-phosphinomethylmalic acid synthase from Streptomyces hygroscopicus SF-1293. J. Antibiot. (Tokyo) 41 (1988) 1057-1065. [PMID: 3170341]
3. Eliot, A.C., Griffin, B.M., Thomas, P.M., Johannes, T.W., Kelleher, N.L., Zhao, H. and Metcalf, W.W. Cloning, expression, and biochemical characterization of Streptomyces rubellomurinus genes required for biosynthesis of antimalarial compound FR900098. Chem. Biol. 15 (2008) 765-770. [PMID: 18721747]
Accepted name: acyl-CoA:acyl-CoA alkyltransferase
Reaction: 2 an acyl-CoA + H2O = a (2R)-2-alkyl-3-oxoalkanoate + 2 CoA
Other name(s): oleA (gene name)
Systematic name: acyl-CoA:acyl-CoA alkyltransferase [(2R)-2-alkyl-3-oxoalkanoate-forming]
Comments: The enzyme, found in certain bacterial species, catalyses a head-to-head non-decarboxylative Claisen condensation of two acyl-CoA molecules, resulting in formation of a 2-alkyl-3-oxoalkanoic acid. It is part of a pathway for the production of olefins.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Sukovich, D.J., Seffernick, J.L., Richman, J.E., Hunt, K.A., Gralnick, J.A. and Wackett, L.P. Structure, function, and insights into the biosynthesis of a head-to-head hydrocarbon in Shewanella oneidensis strain MR-1. Appl. Environ. Microbiol. 76 (2010) 3842-3849. [PMID: 20418444]
2. Frias, J.A., Richman, J.E., Erickson, J.S. and Wackett, L.P. Purification and characterization of OleA from Xanthomonas campestris and demonstration of a non-decarboxylative Claisen condensation reaction. J. Biol. Chem. 286 (2011) 10930-10938. [PMID: 21266575]
3. Goblirsch, B.R., Frias, J.A., Wackett, L.P. and Wilmot, C.M. Crystal structures of Xanthomonas campestris OleA reveal features that promote head-to-head condensation of two long-chain fatty acids. Biochemistry 51 (2012) 4138-4146. [PMID: 22524624]
4. Goblirsch, B.R., Jensen, M.R., Mohamed, F.A., Wackett, L.P. and Wilmot, C.M. Substrate trapping in crystals of the thiolase OleA identifies three channels that enable long chain olefin biosynthesis. J. Biol. Chem. 291 (2016) 26698-26706. [PMID: 27815501]
Accepted name: (R)-citramalate synthase
Reaction: acetyl-CoA + pyruvate + H2O = CoA + (2R)-2-hydroxy-2-methylbutanedioate
Glossary: (2R)-2-hydroxy-2-methylbutanedioate = (2R)-2-methylmalate = (–)-citramalate
3-methyl-2-oxobutanoate =α-ketoisovalerate
2-oxobutanoate = α-ketobutyrate
4-methyl-2-oxopentanoate = α-ketoisocaproate
2-oxohexanoate = α-ketopimelate
2-oxoglutarate = α-ketoglutarate
Other name(s): CimA
Comments: One of the enzymes involved in a pyruvate-derived pathway for isoleucine biosynthesis that is found in some bacterial and archaeal species [1,2]. The enzyme can be inhibited by isoleucine, the end-product of the pathway, but not by leucine [2]. The enzyme is highly specific for pyruvate as substrate, as the 2-oxo acids 3-methyl-2-oxobutanoate, 2-oxobutanoate, 4-methyl-2-oxopentanoate, 2-oxohexanoate and 2-oxoglutarate cannot act as substrate [1,2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Howell, D.M., Xu, H. and White, R.H. (R)-citramalate synthase in methanogenic archaea. J. Bacteriol. 181 (1999) 331-333. [PMID: 9864346]
2. Xu, H., Zhang, Y., Guo, X., Ren, S., Staempfli, A.A., Chiao, J., Jiang, W. and Zhao, G. Isoleucine biosynthesis in Leptospira interrogans serotype 1ai strain 56601 proceeds via a threonine-independent pathway. J. Bacteriol. 186 (2004) 5400-5409. [PMID: 15292141]
Accepted name: 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase
Reaction: an acetyl-[acp] + a 3-oxoacyl-[acp] = a 3-carboxymethyl-3-hydroxy-acyl-[acp] + [acp]
Other name(s): HMG-CoA synthase-like enzyme; aprE (gene name); curD (gene name); corE (gene name); bryR (gene name); pedP (gene name); 3-carboxymethyl-3-hydroxy-acyl-[acyl-carrier protein] synthase
Systematic name: acetyl-[acp]:3-oxoacyl-[acp] C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
Comments: This family of enzymes participates in a process that introduces a methyl branch into nascent polyketide products. The process begins with EC 4.1.1.124, malonyl-[acp] decarboxylase, which converts the common extender unit malonyl-[acp] to acetyl-[acp]. The enzyme is a mutated form of a ketosynthase enzyme, in which a Cys residue in the active site is modified to a Ser residue, leaving the decarboxylase function intact, but nulifying the ability of the enzyme to form a carbon-carbon bond. Next, EC 2.3.3.22, 3-carboxymethyl-3-hydroxy-acyl-[acp] synthase, utilizes the acetyl group to introduce the branch at the β position of 3-oxoacyl intermediates attached to a polyketide synthase, forming a 3-hydroxy-3-carboxymethyl intermediate. This is followed by dehydration catalysed by EC 4.2.1.181, 3-carboxymethyl-3-hydroxy-acyl-[acp] dehydratase (often referred to as an ECH1 domain), leaving a 3-carboxymethyl group and forming a double bond between the α and β carbons. The process concludes with decarboxylation catalysed by EC 4.1.1.125, 4-carboxy-3-alkylbut-2-enoyl-[acp] decarboxylase (often referred to as an ECH2 domain), leaving a methyl branch at the β carbon. The enzymes are usually encoded by a cluster of genes referred to as an "HMGS cassette", based on the similarity of the key enzyme to EC 2.3.3.10, hydroxymethylglutaryl-CoA synthase. While the enzyme is similar to EC 2.3.3.10, it is specific for an [acyl-carrier protein] (acp)-bound donor and does not interact with a CoA substrate as donor.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Erol, O., Schaberle, T.F., Schmitz, A., Rachid, S., Gurgui, C., El Omari, M., Lohr, F., Kehraus, S., Piel, J., Muller, R. and Konig, G.M. Biosynthesis of the myxobacterial antibiotic corallopyronin A. Chembiochem 11 (2010) 1253-1265. [PMID: 20503218]
2. Buchholz, T.J., Rath, C.M., Lopanik, N.B., Gardner, N.P., Hakansson, K. and Sherman, D.H. Polyketide β-branching in bryostatin biosynthesis: identification of surrogate acetyl-ACP donors for BryR, an HMG-ACP synthase. Chem. Biol. 17 (2010) 1092-1100. [PMID: 21035732]
3. Grindberg, R.V., Ishoey, T., Brinza, D., Esquenazi, E., Coates, R.C., Liu, W.T., Gerwick, L., Dorrestein, P.C., Pevzner, P., Lasken, R. and Gerwick, W.H. Single cell genome amplification accelerates identification of the apratoxin biosynthetic pathway from a complex microbial assemblage. PLoS One 6 (2011) e18565. [PMID: 21533272]
4. Maloney, F.P., Gerwick, L., Gerwick, W.H., Sherman, D.H. and Smith, J.L. Anatomy of the β-branching enzyme of polyketide biosynthesis and its interaction with an acyl-ACP substrate. Proc. Natl. Acad. Sci. USA 113 (2016) 10316-10321. [PMID: 27573844]
5. Slocum, S.T., Lowell, A.N., Tripathi, A., Shende, V.V., Smith, J.L. and Sherman, D.H. Chemoenzymatic dissection of polyketide β-branching in the bryostatin pathway. Methods Enzymol. 604 (2018) 207-236. [PMID: 29779653]