Beta-ketoacyl-ACP synthase 2 (KasB) (KasB)

Beta-ketoacyl-ACP synthase 2 (KasB) is a critical enzyme in the Fatty Acid Synthase II (FAS-II) system of Mycobacterium tuberculosis, the causative agent of tuberculosis (NIH, 2002). It is specifically responsible for the final elongation steps of the meromycolic acid chain, producing long-chain fatty acids (averaging 54 carbons) that are essential components of the mycobacterial cell wall (NIH, 2002; NIH, 2013). Unlike KasA, which initiates the elongation process, KasB is required for the full extension of these chains, which maintains the bacterium's characteristic acid-fastness and structural integrity (NIH, 2005). Deletion of the kasB gene results in shortened mycolic acids and an attenuated phenotype that can persist in a subclinical state without causing active disease, making it a key factor in pathogenesis and persistence (NIH, 2005). KasB is considered a promising therapeutic target because its inhibition disrupts cell wall assembly and increases the bacterium's sensitivity to other antibiotics like rifampicin (NIH, 2005; NIH, 2013). Several small molecules, including thiolactomycin and cerulenin, have been identified as inhibitors that target the enzyme's catalytic activity (NIH, 2001; NIH, 2002).

Other names

3-oxoacyl-[acyl-carrier-protein] synthase 2Beta-ketoacyl-acyl carrier protein synthase IIRv2246

KasB catalyzes the condensation of malonyl-ACP with long-chain acyl-ACP substrates in the FAS-II pathway; inhibitors like thiolactomycin bind to the active site to block this elongation step, thereby disrupting mycolic acid synthesis (NIH, 2001; NIH, 2013).