Reaction: 4-methyl-2-oxopentanoate + malonyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine = 5-methyl-3-oxohexanoyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + 2 CO2 (overall reaction)
(1a) 4-methyl-2-oxopentanoate + a [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine = -a [lipoyl-carrier protein]-N6-[(3-methyl-2-oxobutanoyl)-(R)-lipoyl]-L-lysine + CO2
(1b) a [lipoyl-carrier protein]-N6-[(3-methyl-2-oxobutanoyl)-(R)-lipoyl]-L-lysine + malonyl-[acp] = 5-methyl-3-oxohexanoyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + CO2
Glossary: 4-methyl-2-oxopentanoate = 2-oxoisocaproate
Other name(s): nasB (gene name)
Systematic name: branched-chain 2-oxoacid:malonyl-[acyl-carrier protein] acyltransferase
Comments: The enzyme, characterized from an environmental DNA sample and expressed in Paraburkholderia graminis, is a complex enzyme whose purpose is to divert branched-chain 2-oxo acids to production of branched-chain N-acyl amino acids by producing branched 3-oxoacyl-[acp] molecules. NasB accepts branched-chain 2-oxoacids such as 4-methyl-2-oxopentanoate, and catalyses a decarboxylative transfer to a thiamine diphosphate cofactor, followed by a transfer to a lipoyl cofactor, and finally a second decarboxylative transfer to the malonyl-[acp] acceptor. The products, such as 5-methyl-3-oxohexanoyl-[acp], can be extended by the fatty acid synthase system to form branched long-chain fatty-acyl-[acp] molecules, which serve as substrates for EC 2.3.1.327, long-chain acyl-[acp]:L-phenylalanine N-acyltransferase (NasA). During the reaction the lipoyl cofactor is reduced to dihydrolipoyl, which must be oxidized back to lipoyl by an unknown enzyme.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Craig, J.W. and Brady, S.F. Discovery of a metagenome-derived enzyme that produces branched-chain acyl-(acyl-carrier-protein)s from branched-chain α-keto acids. Chembiochem 12 (2011) 1849-1853. [PMID: 21714057]