Diverse unsaturated fatty acids bypass loss of FabH-catalysed initiation of fatty acid synthesis in Enterococcus faecalis.

The initiation reaction of fatty acid synthesis in Enterococcus faecalis is catalysed by the FabH 3-ketoacyl-acyl carrier protein (ACP) synthase III. Deletion of the fabH gene seriously impaired growth but failed to fully block de novo fatty acid synthesis. We report that exogenous medium-chain unsaturated fatty acids restore normal growth of a ∆fabH strain and upon elongation provide substrates for synthesis of functional membrane phospholipid bilayers. Entry of these acids into the elongation pathway was aided by increased expression of the AcpA ACP of fatty acid synthesis and/or of the phosphate: ACP acyltransferase PlsX. The efficacy of incorporation of these acids increased with increasing chain length. Coordinate overexpression of E. faecalis AcpA and PlsX or expression of the Lactococcus lactis PlsX allowed elongation of the short-chain octanoic acid to provide unsaturated fatty acids for growth of the ∆fabH strain. We also tested the abilities of the two long-chain β-ketoacyl-ACP synthases, FabO and FabF, in elongation of exogenous unsaturated fatty acids.