Beta-ketoacyl-ACP synthase III (FabH)

Beta-ketoacyl-ACP synthase III (FabH) is a pivotal enzyme in Mycobacterium tuberculosis that serves as the link between the fatty acid synthase I (FAS-I) and fatty acid synthase II (FAS-II) pathways (UniProt P9WNG3). It catalyzes the initial condensation of acetyl-CoA with malonyl-acyl carrier protein (ACP) to form acetoacetyl-ACP, a precursor for the long-chain fatty acids required for mycolic acid synthesis (PubMed PMID: 10411905). Mycolic acids are essential components of the mycobacterial cell wall, contributing to its impermeability and resistance to host immune responses and antibiotics (PubMed PMID: 15659518). Since FabH is essential for the survival of M. tuberculosis and has no human ortholog—as humans utilize a single-polypeptide FAS-I system—it represents a promising target for the development of new antitubercular agents (PubMed PMID: 21539350). Inhibition of this enzyme, by compounds such as thiolactomycin, leads to the disruption of cell wall biogenesis and eventual bacterial lysis (PubMed PMID: 11137816).

Other names

3-oxoacyl-[acyl-carrier-protein] synthase 3KAS IIIBeta-ketoacyl-acyl carrier protein synthase III3-oxoacyl-ACP synthase IIIAcyl-ACP synthase

Inhibition of the condensation reaction between acetyl-CoA and malonyl-ACP, thereby blocking the initiation of the fatty acid synthase II (FAS-II) pathway and preventing the synthesis of mycolic acids.