Beta-ketoacyl-ACP synthase 2 (KAS II) (KAS II)

Beta-ketoacyl-ACP synthase 2 (KAS II), also known as FabF, is a vital enzyme in the bacterial Type II fatty acid synthesis (FAS II) pathway (UniProt: P0AAI5). It catalyzes the condensation of malonyl-ACP with an acyl-ACP to elongate fatty acid chains, a process essential for maintaining bacterial membrane integrity and function (PubMed: 15522877). KAS II is particularly important for the thermal regulation of membrane fluidity, as it facilitates the elongation of palmitoleoyl-ACP to cis-vaccenoyl-ACP (UniProt: P0AAI5). Because the bacterial FAS II system is structurally distinct from the human Type I fatty acid synthase (FAS I), KAS II is considered a high-value target for the development of novel antibiotics (PubMed: 17051150). Natural products such as platensimycin and platencin act as potent, selective inhibitors of KAS II, demonstrating significant efficacy against multi-drug resistant pathogens, including Methicillin-resistant Staphylococcus aureus (MRSA) (PubMed: 17051150, PubMed: 18328078). However, the clinical advancement of these inhibitors has been hindered by challenges such as poor oral bioavailability and the potential for rapid resistance development (PubMed: 21534557).

Other names

3-oxoacyl-[acyl-carrier-protein] synthase 2FabFBeta-ketoacyl-acyl carrier protein synthase IIKASIIKAS II

Inhibition of the condensation reaction between malonyl-ACP and an acyl-ACP, preventing the elongation of fatty acid chains essential for bacterial membrane integrity (PubMed: 17051150).