Enoyl-[acyl-carrier-protein] reductase (NADH) (FabI) (FabI)

Bacterial enoyl-acyl carrier protein reductase, commonly known as FabI, is a critical enzyme in the Type II Fatty Acid Synthase (FAS II) pathway, which is essential for bacterial cell membrane and wall synthesis (UniProt P0AEK4) [1]. Unlike humans who utilize a single large multifunctional protein (FAS I), bacteria rely on a series of discrete, individual enzymes to synthesize fatty acids (PMID: 21663457) [2]. FabI catalyzes the final, rate-limiting step of the fatty acid elongation cycle, reducing the double bond of the enoyl-ACP substrate to form an acyl-ACP using NADH or NADPH as a cofactor (PubMed: 22432845) [3]. Because of the structural differences between bacterial FAS II and human FAS I, this enzyme is a highly attractive target for the development of narrow-spectrum and broad-spectrum antibiotics (PMID: 19292014) [4]. Drugs such as isoniazid and ethionamide target the FabI homolog (InhA) in Mycobacterium tuberculosis, while newer agents like afabicin are being developed to treat staphylococcal infections (PubChem CID 6048) [5]. Inhibition of this enzyme leads to the depletion of essential fatty acids, resulting in the loss of membrane integrity and bacterial cell death (PMID: 26806081) [6].

Other names

Enoyl-ACP reductaseInhAFabKFabLFabVNADH-dependent enoyl-ACP reductaseTrans-2-enoyl-ACP reductase

Inhibition of the enoyl-acyl carrier protein reductase enzyme, which prevents the reduction of the trans-double bond in the fatty acid chain, thereby halting the elongation cycle of bacterial fatty acid biosynthesis (PMID: 22432845).