Beta-ketoacyl-acyl carrier protein synthase 1 (KasA) (KasA)

Beta-ketoacyl-acyl carrier protein synthase 1 (KasA) is a pivotal enzyme within the Fatty Acid Synthase II (FAS-II) complex of Mycobacterium tuberculosis, the causative agent of tuberculosis (UniProt P9WNG3). It plays a central role in the biosynthesis of mycolic acids by catalyzing the condensation of malonyl-acyl carrier protein (ACP) with growing acyl-ACP chains to facilitate fatty acid elongation (Schaeffer et al., 2001, JBC). These mycolic acids are indispensable for the formation of the mycobacterial cell envelope, which serves as a robust physical barrier against antibiotics and host-mediated killing. Due to its essentiality for bacterial viability and its absence in humans, KasA is a prominent target for drug discovery efforts aimed at treating both drug-sensitive and multi-drug resistant tuberculosis. Small-molecule inhibitors, including thiolactomycin and novel indazole-based compounds like GSK3011724A, bind to the KasA active site to block its catalytic activity, effectively halting cell wall production and inducing bacterial death (Abrahams et al., 2016, Nature Communications).

Other names

3-oxoacyl-[acyl-carrier-protein] synthase 1KAS IBeta-ketoacyl-ACP synthase 1Beta-ketoacyl-acyl carrier protein synthase I

Inhibition of the condensation reaction between malonyl-acyl carrier protein (ACP) and an acyl-ACP primer, thereby blocking the elongation of long-chain fatty acids essential for mycolic acid synthesis (Abrahams et al., 2016, Nature Communications).