3-oxoacyl-[acyl-carrier-protein] synthase 1 (KasA) (KasA)

3-oxoacyl-[acyl-carrier-protein] synthase 1, frequently referred to as KasA or mtFabB, is an essential enzyme within the Type II Fatty Acid Synthase (FAS-II) system of Mycobacterium tuberculosis (UniProt: P9WNG3). It plays a pivotal role in the elongation of fatty acid chains by catalyzing the Claisen condensation of acyl-ACP with malonyl-ACP, a process fundamental for the production of long-chain mycolic acids (PubMed: 10444070). These acids constitute the protective, waxy cell wall of the bacterium and are vital for its survival and virulence. Because the FAS-II pathway is absent in humans, who utilize a distinct FAS-I system, KasA is a prominent target for the development of narrow-spectrum antibiotics (PubMed: 24560162). Inhibitors such as thiolactomycin and synthetic indole-2-carboxamides bind to the enzyme's active site, effectively disrupting cell wall integrity and leading to bacterial death (PubMed: 21113167). Clinical interest in KasA is further driven by its role in drug resistance, as specific mutations in the kasA gene have been identified in isoniazid-resistant strains of M. tuberculosis (PubMed: 9537321).

Other names

mtFabBBeta-ketoacyl-ACP synthase IKAS I3-oxoacyl-ACP synthase 1Beta-ketoacyl-acyl carrier protein synthase 1

Inhibition of the Claisen condensation reaction between malonyl-ACP and an acyl-ACP primer in the FAS-II elongation cycle.