Reaction: a 4-carboxy-3-alkylbut-2-enoyl-[acp] = a 3-alkylbut-2-enoyl-[acp] + CO2
Other name(s): aprG (gene name); corG (gene name); pedI (gene name); mupK (gene name); 3-carboxymethyl-alk-2-enyl-[acyl-carrier protein] decarboxylase
Systematic name: 4-carboxy-3-alkylbut-2-enoyl-[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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Geders, T.W., Gu, L., Mowers, J.C., Liu, H., Gerwick, W.H., Hakansson, K., Sherman, D.H. and Smith, J.L. Crystal structure of the ECH2 catalytic domain of CurF from Lyngbya majuscula. Insights into a decarboxylase involved in polyketide chain β-branching. J. Biol. Chem. 282 (2007) 35954-35963. [PMID: 17928301]
2. 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]
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]