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

Bacterial enoyl-ACP reductase (FabI) is a critical enzyme in the Type II fatty acid synthesis (FAS II) pathway, which is essential for the production of membrane phospholipids in many bacterial species (Wikipedia, 2024). It catalyzes the final, rate-limiting reduction step in the fatty acid elongation cycle, converting trans-2-enoyl-ACP to acyl-ACP using NADH or NADPH as a cofactor (NIH, 2013). Because the FAS II system is structurally and mechanistically distinct from the mammalian Type I fatty acid synthase, FabI serves as a highly selective target for antibacterial drug discovery with minimal cross-reactivity in humans (Frontiers in Microbiology, 2020). Well-known inhibitors include the biocidal agent triclosan and the front-line antitubercular drug isoniazid, the latter of which targets the FabI homolog InhA in Mycobacterium tuberculosis (ACS, 2005). Despite its validation as a target, the clinical utility of FabI inhibitors is often limited by the rapid emergence of resistance through single-point mutations and the presence of alternative enoyl-reductase isoforms, such as FabK or FabV, in certain pathogens (NIH, 2003). Recent drug development efforts, such as the prodrug afabicin, aim to exploit FabI's essentiality in specific pathogens like Staphylococcus aureus to treat multidrug-resistant infections (Patsnap, 2024).

Other names

ENRtrans-2-enoyl-ACP reductaseInhAFabI1Enoyl-acyl carrier protein reductase

Inhibition of the final reduction step in the bacterial fatty acid synthesis (FAS II) elongation cycle, preventing the conversion of trans-2-enoyl-ACP to acyl-ACP and leading to the depletion of essential membrane components (NIH, 2013).