Reaction: (1) a long-chain acyl-CoA + 3 methylmalonyl-CoA + 6 NADPH + 6 H+ + mycocerosate synthase = a trimethylated-mycocerosoyl-[mycocerosate synthase] + 4 CoA + 3 CO2 + 6 NADP+ + 3 H2O
(2) a long-chain acyl-CoA + 4 methylmalonyl-CoA + 8 NADPH + 8 H+ + mycocerosate synthase = a tetramethylated-mycocerosoyl-[mycocerosate synthase] + 5 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)
Systematic name: long-chain acyl-CoA:methylmalonyl-CoA C-acyltransferase (mycocerosate-forming)
Comments: This mycobacterial enzyme loads long-chain fatty acyl groups from their CoA esters and extends them 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 products remain bound to the enzyme and require 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]
3. Trivedi, O.A., Arora, P., Vats, A., Ansari, M.Z., Tickoo, R., Sridharan, V., Mohanty, D. and Gokhale, R.S. Dissecting the mechanism and assembly of a complex virulence mycobacterial lipid. Mol. Cell 17 (2005) 631-643. [PMID: 15749014]
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