3-oxoacyl-[acyl-carrier-protein] synthase 2 (FabF)

3-oxoacyl-[acyl-carrier-protein] synthase 2, commonly known as FabF, is a key enzyme in the bacterial Type II fatty acid synthesis (FAS II) pathway. It catalyzes the condensation of an acyl-acyl carrier protein (ACP) with malonyl-ACP, a critical step that extends the growing fatty acid chain by two carbon units. This enzyme is essential for maintaining the structural integrity of the bacterial cell membrane and plays a specialized role in the thermal regulation of fatty acid composition. Because the FAS II system is composed of discrete enzymes and is structurally distinct from the multifunctional human Type I FAS system, FabF is considered a highly attractive target for the development of novel antibiotics. Several natural product inhibitors, including platensimycin and cerulenin, have been identified that potently inhibit FabF by binding to its active site. While these compounds show significant antibacterial activity in laboratory settings, their clinical development has been challenged by poor pharmacological properties and the potential for rapid emergence of resistance. Ongoing research aims to optimize these inhibitors to address the growing threat of multidrug-resistant bacterial infections.

Other names

3-oxoacyl-[acyl-carrier-protein] synthase IIBeta-ketoacyl-ACP synthase IIKAS IIKAS2Beta-ketoacyl-acyl carrier protein synthase II

Inhibition of the condensation step in the bacterial Type II fatty acid synthesis (FAS II) pathway by binding to the enzyme's active site, thereby preventing the elongation of fatty acid chains and disrupting membrane integrity.