Bacterial β-ketoacyl-acyl carrier protein synthase III (FabH) as a target for novel antibacterial agents design.

Abstract

In bacterial type II fatty acid biosynthesis (FAS-II), β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) initiates the first condensation of acyl-CoA and malonyl-ACP to form acetoacetyl-ACP. Its key role for organism survival and specificity to bacteria make it as an essential target for the discovery of novel antibacterial agents. Over the last decade, several structures of FabH from diverse microorganisms have been solved, giving detailed information about the three-dimensional features of the catalytic pocket. This has facilitated the rational design of FabH inhibitors, which provides a framework for future development of antibiotics against multi-drug resistant strains. This review covers recent advances in the biochemical and structural research of FabH and updates the main families of related inhibitors.