Reaction: (1) a long-chain acyl-[mycocerosic acid synthase] + 3 methylmalonyl-CoA + 6 NADPH + 6 H+ = a trimethylated-mycocerosoyl-[mycocerosate synthase] + 3 CoA + 3 CO2 + 6 NADP+ + 3 H2O
(2) a long-chain acyl-[mycocerosic acid synthase] + 4 methylmalonyl-CoA + 8 NADPH + 8 H+ = a tetramethylated-mycocerosoyl-[mycocerosate synthase] + 4 CoA + 4 CO2 + 8 NADP+ + 4 H2O
Glossary: mycocerosic acid = a long-chain fatty acid with 3 or 4 methyl branches at positions 2,4,6 or 2,4,6,8, respectively. The carbon atoms bearing the methyl groups have the (R)-configuration.
Other name(s): mas (gene name); mycocerosic acid synthase; acyl-CoA:methylmalonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing); long-chain acyl-CoA:methylmalonyl-CoA C-acyltransferase (mycocerosate-forming)
Systematic name: long-chain acyl-[mycocerosic acid synthase]:methylmalonyl-CoA C-acyltransferase (mycocerosate-forming)
Comments: The enzyme, characterized from mycobacteria, is loaded with a long-chain acyl moiety by EC 18.104.22.168, long-chain fatty acid adenylyltransferase FadD28, and elongates it by incorporation of three or four methylmalonyl (but not malonyl) residues, to form tri- or tetramethyl-branched fatty-acids, respectively, such as 2,4,6,8-tetramethyloctacosanoate (C32-mycocerosate). Since the enzyme lacks a thioesterase domain, the product remains bound and requires additional enzyme(s) for removal. Even though the enzyme can accept C6 to C20 substrates in vitro, it prefers to act on C14-C20 substrates in vivo.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 95229-19-9
1. Rainwater, D.L. and Kollattukudy, P.E. Fatty acid biosynthesis in Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guérin. Purification and characterization of a novel fatty acid synthase, mycocerosic acid synthase, which elongates n-fatty acyl-CoA with methylmalonyl-CoA. J. Biol. Chem. 260 (1985) 616-623. [PMID: 3880746]
2. Mathur, M. and Kolattukudy, P.E. Molecular cloning and sequencing of the gene for mycocerosic acid synthase, a novel fatty acid elongating multifunctional enzyme, from Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guerin. J. Biol. Chem. 267 (1992) 19388-19395. [PMID: 1527058]
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