Beta-ketoacyl-acyl-carrier-protein synthase I and Beta-ketoacyl-acyl-carrier-protein synthase II (KAS I (for synthase I), KAS II (for synthase II); also FabB (KAS I), FabF (KAS II))

Beta-ketoacyl-acyl-carrier-protein synthases I and II are essential enzymes involved in the chain elongation steps of fatty acid biosynthesis, operating in bacteria and plants (as type II fatty acid synthase pathway enzymes)[1][3][6]. They catalyze the condensation of acyl carrier protein–bound acyl groups with malonyl-ACP, extending fatty acid chains by two carbon units per cycle via a decarboxylative Claisen condensation mechanism. KAS I (sometimes called FabB) and KAS II (FabF) have overlapping but distinct substrate specificities, controlling the length and degree of unsaturation in fatty acids[2][3][5]. These enzymes are important targets for antibacterial drug discovery due to their essential role in bacterial cell membrane biosynthesis and their structural differences from human fatty acid synthases, allowing for selective inhibition by compounds such as platencin, platensimycin, cerulenin, and thiolactomycin[4][6]. KAS II, for example, is crucial for the elongation of palmitoleic acid to cis-vaccenic acid, especially under cold conditions in Escherichia coli[3]. Inhibiting these enzymes disrupts bacterial growth and survival, underlining their relevance as therapeutic targets.

Other names

Beta-ketoacyl-ACP synthase IBeta-ketoacyl-ACP synthase II3-oxoacyl-ACP synthase I3-oxoacyl-ACP synthase IIKAS IKAS IIFabB (for KAS I)FabF (for KAS II)(Z)-hexadec-11-enoyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein] C-acyltransferase (for KAS II)

Inhibition of fatty acid elongation by binding to the active site and blocking the Claisen condensation reaction; Covalent or non-covalent inhibition of active-site cysteine; Disruption of membrane synthesis in bacteria