ID 2.3.3.22 DE 3-carboxymethyl-3-hydroxy-acyl-[ACP] synthase. AN 3-carboxymethyl-3-hydroxy-acyl-[acyl-carrier protein] synthase. CA a 3-oxoacyl-[ACP] + acetyl-[ACP] + H2O = a 3-carboxymethyl-3-hydroxy- CA acyl-[ACP] + holo-[ACP] + H(+). CC -!- This family of enzymes participates in a process that introduces a CC methyl branch into nascent polyketide products. CC -!- The process begins with EC 4.1.1.124 which converts the common CC extender unit malonyl-[ACP] to acetyl-[ACP]. The enzyme is a mutated CC form of a ketosynthase enzyme, in which a Cys residue in the active CC site is modified to a Ser residue, leaving the decarboxylase function CC intact, but nulifying the ability of the enzyme to form a carbon- CC carbon bond. CC -!- Next, EC 2.3.3.22 utilizes the acetyl group to introduce the branch CC at the beta position of 3-oxoacyl intermediates attached to a CC polyketide synthase, forming a 3-hydroxy-3-carboxymethyl CC intermediate. CC -!- This is followed by dehydration catalyzed by EC 4.2.1.181 (often CC referred to as an ECH1 domain), leaving a 3-carboxymethyl group and CC forming a double bond between the alpha and beta carbons. CC -!- The process concludes with decarboxylation catalyzed by EC 4.1.1.125 CC (often referred to as an ECH2 domain), leaving a methyl branch at the CC beta carbon. CC -!- The enzymes are usually encoded by a cluster of genes referred to as CC an "HMGS cassette", based on the similarity of the key enzyme to CC EC 2.3.3.10, hydroxymethylglutaryl-CoA synthase. CC -!- While the enzyme is similar to EC 2.3.3.10, it is specific for an CC [acyl-carrier protein] (ACP)-bound donor and does not interact with a CC CoA substrate as donor. //