Reaction: a long-chain acyl-CoA + 3 (R)-methylmalonyl-CoA + 6 NADPH + 6 H+ + holo-[mycolipanoate synthase] = mycolipanoyl-[mycolipanoate synthase] + 4 CoA + 3 CO2 + 6 NADP+ + 3 H2O
Glossary: mycolipanoic acid = (2S,4S,6S)-2,4,6-trimethyl-very-long-chain fatty acid
Other name(s): msl3 (gene name); Pks3/4; mycolipanoic acid synthase
Systematic name: long-chain acyl-CoA:methylmalonyl-CoA C-acyltransferase (mycolipanoate-forming)
Comments: This mycobacterial enzyme accepts long-chain fatty acyl groups from their CoA esters and extends them by incorporation of three methylmalonyl (but not malonyl) residues, forming trimethyl-branched fatty-acids such as (2S,4S,6S)-2,4,6-trimethyltetracosanoate (C27-mycolipanoate). Since the enzyme lacks a thioesterase domain, the product remains bound to the enzyme and requires additional enzyme(s) for removal.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
1. Sirakova, T.D., Thirumala, A.K., Dubey, V.S., Sprecher, H. and Kolattukudy, P.E. The Mycobacterium tuberculosis pks2 gene encodes the synthase for the hepta- and octamethyl-branched fatty acids required for sulfolipid synthesis. J. Biol. Chem. 276 (2001) 16833-16839. [PMID: 11278910]
2. Dubey, V.S., Sirakova, T.D. and Kolattukudy, P.E. Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and causes cell aggregation. Mol. Microbiol. 45 (2002) 1451-1459. [PMID: 12207710]