Reaction: malonyl-[acp] = acetyl-[acp] + CO2
Other name(s): decarboxylative ketosynthase; bryQ (gene name); mupG (gene name); pksF (gene name); curC (gene name); jamG (gene name); pedM (gene name)
Systematic name: malonyl-[acyl-carrier protein] carboxy-lyase
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. cf. EC 4.1.1.87, malonyl-[malonate decarboxylase] decarboxylase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Simunovic, V. and Muller, R. 3-hydroxy-3-methylglutaryl-CoA-like synthases direct the formation of methyl and ethyl side groups in the biosynthesis of the antibiotic myxovirescin A. Chembiochem 8 (2007) 497-500. [PMID: 17330904]
2. Wu, J., Hothersall, J., Mazzetti, C., O'Connell, Y., Shields, J.A., Rahman, A.S., Cox, R.J., Crosby, J., Simpson, T.J., Thomas, C.M. and Willis, C.L. In vivo mutational analysis of the mupirocin gene cluster reveals labile points in the biosynthetic pathway: the "leaky hosepipe" mechanism. Chembiochem 9 (2008) 1500-1508. [PMID: 18465759]
3. 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]