SCO6564, a novel 3-ketoacyl acyl carrier protein synthase III, contributes in fatty acid synthesis in Streptomyces coelicolor

The genus Streptomyces comprises gram-positive bacteria that produce large numbers of secondary metabolites, which have promising commercial applications and deserve extensive study. Most bacteria synthesize fatty acids using a type II fatty acid synthase, with each step catalyzed by a discrete protein. Fatty acid synthesis has been intensively studied in the model strain Streptomyces coelicolor, in which 3-ketoacyl-acyl carrier protein synthase III (KAS III, FabH) is essential for growth and fatty acid biosynthesis. In this study, the FabH homolog SCO6564 (named FabH2) was identified in the S. coelicolor genome by BLAST analysis. The expression of fabH2 restored the growth of Ralstonia solanacearum fabH mutant and made the mutant produce small amounts of branched-chain fatty acids. FabH2 could condense various substrates, including straight-chain and branched-chain acyl-CoAs, with malonyl-acyl carrier protein to initiate fatty acid synthesis in in vitro assays. The fabH2 deletion did not cause significant changes in the growth or fatty acid composition of S. coelicolor, indicating that fabH2 is nonessential for growth or fatty acid synthesis. However, fabH2 overexpression reduced the blue-pigmented actinorhodin production. Phylogenetic analysis of KAS III from different bacteria revealed that FabH2 belongs to a novel group of FabH-type, which is ubiquitous in Streptomyces spp.