Beta-ketoacyl-acyl carrier protein synthase 1 (KAS I) (KAS I)

Beta-ketoacyl-acyl carrier protein synthase 1 (KAS I), encoded by the fabB gene, is a vital enzyme within the bacterial Type II fatty acid synthesis (FAS II) system (UniProt: P0A953). It facilitates the Claisen condensation of malonyl-acyl carrier protein (ACP) with an acyl-ACP to extend the fatty acid chain by two carbons (PMID: 11210171). KAS I is uniquely essential for the biosynthesis of unsaturated fatty acids in many bacteria, as it is the primary enzyme capable of elongating the cis-3-decenoyl-ACP intermediate (PMID: 12570782). This enzyme is a prominent target for antibacterial drug development because the FAS II pathway is distinct from the human Type I FAS system, allowing for selective toxicity (PMID: 21370994). Natural products such as cerulenin and thiolactomycin act as potent inhibitors by binding to the active site and disrupting the condensation reaction (PMID: 11210171). Inhibition of KAS I leads to the depletion of membrane lipids, resulting in bacterial growth arrest and cell death. Due to its role in essential lipid metabolism, KAS I remains a key focus in the search for novel treatments against multidrug-resistant pathogens.

Other names

3-oxoacyl-[acyl-carrier-protein] synthase 1FabBBeta-ketoacyl-ACP synthase IKasAKASI

Inhibition of the Claisen condensation between malonyl-acyl carrier protein (ACP) and acyl-ACP, preventing fatty acid chain elongation and disrupting bacterial membrane synthesis.