|Superclasses:||Reactions Classified By Conversion Type → Simple Reactions → Chemical Reactions → Protein-Modification Reactions|
|Reactions Classified By Substrate → Macromolecule Reactions → Protein-Reactions → Protein-Modification Reactions|
In Pathway: fatty acid biosynthesis initiation I
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
Mass balance status: Balanced.
Enzyme Commission Primary Name for 188.8.131.52: [acyl-carrier-protein] S-malonyltransferase
Enzyme Commission Synonyms for 184.108.40.206: [acyl carrier protein]malonyltransferase, FabD, malonyl coenzyme A-acyl carrier protein transacylase, malonyl transacylase, malonyl transferase, malonyl-CoA-acyl carrier protein transacylase, malonyl-CoA:[acyl-carrier-protein] S-malonyltransferase, malonyl-CoA:ACP transacylase, malonyl-CoA:ACP-SH transacylase, malonyl-CoA:AcpM transacylase, malonyl-CoA:acyl carrier protein transacylase, malonyl-CoA:acyl-carrier-protein transacylase, malonyl-CoA/dephospho-CoA acyltransferase, MAT, MCAT, MdcH
Enzyme Commission Primary Name for 220.127.116.11: fatty-acid synthase
Enzyme Commission Synonyms for 18.104.22.168: FASN (gene name)
Enzyme Commission Primary Name for 22.214.171.124: fatty-acyl-CoA synthase
Enzyme Commission Synonyms for 126.96.36.199: yeast fatty acid synthase, FAS1 (gene name), FAS2 (gene name)
This reaction prepares malonate for use in the biosynthesis of fatty acids. The energy-rich bonds in acyl-CoAs and acyl-ACPs are identical.
Enzyme Commission Summary for 188.8.131.52:
This enzyme, along with EC 184.108.40.206, [acyl-carrier-protein] S-acetyltransferase, is essential for the initiation of fatty-acid biosynthesis in bacteria. This enzyme also provides the malonyl groups for polyketide biosynthesis [Szafranska02]. The product of the reaction, malonyl-ACP, is an elongation substrate in fatty-acid biosynthesis. In Mycobacterium tuberculosis, holo-ACP (the product of EC 220.127.116.11, holo-[acyl-carrier-protein] synthase) is the preferred substrate [Kremer01]. This enzyme also forms part of the multienzyme complexes EC 18.104.22.168, biotin-independent malonate decarboxylase and EC 22.214.171.124, biotin-dependent malonate decarboxylase. Malonylation of ACP is immediately followed by decarboxylation within the malonate-decarboxylase complex to yield acetyl-ACP, the catalytically active species of the decarboxylase [Dimroth97]. In the enzyme from Klebsiella pneumoniae, methylmalonyl-CoA can also act as a substrate but acetyl-CoA cannot [Hoenke99] whereas the enzyme from Pseudomonas putida can use both as substrates [Chohnan98]. The ACP subunit found in fatty-acid biosynthesis contains a pantetheine-4'-phosphate prosthetic group; that from malonate decarboxylase also contains pantetheine-4'-phosphate but in the form of a 2'-(5-triphosphoribosyl)-3'-dephospho-CoA prosthetic group.
Enzyme Commission Summary for 126.96.36.199:
The animal enzyme is a multi-functional protein catalysing the reactions of EC 188.8.131.52, [acyl-carrier-protein] S-acetyltransferase, EC 184.108.40.206, [acyl-carrier-protein] S-malonyltransferase, EC 220.127.116.11, β-ketoacyl-[acyl-carrier-protein] synthase I, EC 18.104.22.168, 3-oxoacyl-[acyl-carrier-protein] reductase, EC 22.214.171.124, 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 126.96.36.199, enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) and EC 188.8.131.52, oleoyl-[acyl-carrier-protein] hydrolase. cf. EC 184.108.40.206, fatty-acyl-CoA synthase.
Enzyme Commission Summary for 220.127.116.11:
The enzyme from yeasts (Ascomycota and Basidiomycota) is a multi-functional protein complex composed of two subunits. One subunit catalyses the reactions EC 18.104.22.168, 3-oxoacyl-[acyl-carrier-protein] reductase and EC 22.214.171.124, β-ketoacyl-[acyl-carrier-protein] synthase I, while the other subunit catalyses the reactions of EC 126.96.36.199, [acyl-carrier-protein] S-acetyltransferase, EC 188.8.131.52, [acyl-carrier-protein] S-malonyltransferase, EC 184.108.40.206, 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, EC 220.127.116.11, enoyl-[acyl-carrier-protein] reductase (NADPH, Si-specific) and EC 18.104.22.1689, (R)-3-hydroxyacid-ester dehydrogenase. The enzyme differs from the animal enzyme (EC 22.214.171.124) in that the enoyl reductase domain requires FMN as a cofactor, and the ultimate product is an acyl-CoA (usually palmitoyl-CoA) instead of a free fatty acid.
Relationship Links: BRENDA:EC:126.96.36.199 , BRENDA:EC:188.8.131.52 , BRENDA:EC:184.108.40.206 , ENZYME:EC:220.127.116.11 , ENZYME:EC:18.104.22.168 , ENZYME:EC:22.214.171.124 , IUBMB-ExplorEnz:EC:126.96.36.199 , IUBMB-ExplorEnz:EC:188.8.131.52 , IUBMB-ExplorEnz:EC:184.108.40.206
Chohnan98: Chohnan S, Fujio T, Takaki T, Yonekura M, Nishihara H, Takamura Y (1998). "Malonate decarboxylase of Pseudomonas putida is composed of five subunits." FEMS Microbiol Lett 169(1);37-43. PMID: 9851033
Hoenke97: Hoenke S, Schmid M, Dimroth P (1997). "Sequence of a gene cluster from Klebsiella pneumoniae encoding malonate decarboxylase and expression of the enzyme in Escherichia coli." Eur J Biochem 246(2);530-8. PMID: 9208947
Hoenke99: Hoenke S, Dimroth P (1999). "Formation of catalytically active acetyl-S-malonate decarboxylase requires malonyl-coenzyme A:acyl carrier protein transacylase as auxiliary enzyme [corrected]." Eur J Biochem 259(1-2);181-7. PMID: 9914491
Joshi71: Joshi VC, Wakil SJ (1971). "Studies on the mechanism of fatty acid synthesis. XXVI. Purification and properties of malonyl-coenzyme A--acyl carrier protein transacylase of Escherichia coli." Arch Biochem Biophys 1971;143(2);493-505. PMID: 4934182
KeatingeClay03: Keatinge-Clay AT, Shelat AA, Savage DF, Tsai SC, Miercke LJ, O'Connell JD, Khosla C, Stroud RM (2003). "Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase." Structure 11(2);147-54. PMID: 12575934
Kremer01: Kremer L, Nampoothiri KM, Lesjean S, Dover LG, Graham S, Betts J, Brennan PJ, Minnikin DE, Locht C, Besra GS (2001). "Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II." J Biol Chem 276(30);27967-74. PMID: 11373295
Stoops79: Stoops JK, Ross P, Arslanian MJ, Aune KC, Wakil SJ, Oliver RM (1979). "Physicochemical studies of the rat liver and adipose fatty acid synthetases." J Biol Chem 254(15);7418-26. PMID: 457689
Szafranska02: Szafranska AE, Hitchman TS, Cox RJ, Crosby J, Simpson TJ (2002). "Kinetic and mechanistic analysis of the malonyl CoA:ACP transacylase from Streptomyces coelicolor indicates a single catalytically competent serine nucleophile at the active site." Biochemistry 41(5);1421-7. PMID: 11814333
Williamson66: Williamson IP, Wakil SJ (1966). "Studies on the mechanism of fatty acid synthesis. XVII. Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier protein transacylases." J Biol Chem 241(10);2326-32. PMID: 5330116
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