Malonyl-CoA-acyl carrier protein transacylase (MCAT) (MCAT)

Malonyl-CoA-acyl carrier protein transacylase (MCAT), frequently referred to as FabD in bacteria, is a vital enzyme in the Type II fatty acid synthesis (FAS II) pathway (Source: UniProt P0AAI9). It catalyzes the transfer of a malonyl moiety from malonyl-CoA to the acyl carrier protein (ACP), a fundamental step that provides the malonyl-ACP extender units required for fatty acid chain elongation (Source: PubMed 11370614). In humans, MCAT is localized within the mitochondria and plays an essential role in mitochondrial fatty acid synthesis (mtFAS), which is necessary for the lipoylation of key metabolic enzymes and mitochondrial membrane maintenance (Source: PubMed 25449258). Because the bacterial FAS II system is structurally distinct from the human cytosolic FAS I system, FabD is a major target for developing narrow-spectrum and broad-spectrum antibiotics, particularly for treating tuberculosis and malaria (Source: PubMed 19382746). While there are currently no FDA-approved drugs specifically targeting MCAT, several natural products like epigallocatechin gallate and experimental small molecules have shown promise as inhibitors in preclinical research (Source: PubMed 16406471). A significant challenge in targeting this enzyme is maintaining selectivity to avoid disrupting human mitochondrial function while overcoming the propensity for bacterial resistance (Source: PubMed 21901861).

Other names

FabDMalonyltransferase[acyl-carrier-protein] malonyltransferaseMitochondrial malonyl-CoA:ACP transacylaseMalonyl-CoA:ACP transacylase

Inhibition of the transfer of the malonyl group from malonyl-CoA to the thiol group of the acyl carrier protein (ACP), thereby preventing the formation of malonyl-ACP and halting the initiation of fatty acid chain elongation.