IUBMB Enzyme Nomenclature


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, 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, 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, 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-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, hydroxymethylglutaryl-CoA synthase. While the enzyme is similar to EC, 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:


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]

[EC created 2023]

Return to EC 2.3.3 home page
Return to EC 2.3 home page
Return to EC 2 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page