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

Enoyl-[acyl-carrier-protein] reductase [NADH], commonly referred to as FabI, is an essential enzyme within the bacterial Type II fatty acid synthesis (FAS-II) system [4, 12, 16]. It catalyzes the final, rate-limiting reduction step in each fatty acid elongation cycle, converting trans-2-enoyl-ACP to acyl-ACP using NADH as the hydrogen donor [9, 10, 22]. Because this pathway is structurally and mechanistically distinct from the multi-enzyme human FAS-I system, FabI has emerged as a validated and selective target for antimicrobial drug discovery [10, 11, 21]. Clinically relevant drugs like afabicin (Debio 1450) and the biocide triclosan inhibit FabI by binding to its active site and forming a stable ternary complex with the nicotinamide cofactor, which halts membrane biogenesis and leads to bacterial cell death [1, 3, 7]. While it is a promising target for treating infections caused by pathogens such as Staphylococcus aureus, therapeutic efficacy can be challenged by the emergence of chromosomal point mutations or the presence of alternative enoyl-reductase isoforms like FabK, FabL, or FabV in some species [5, 6, 19, 22].

Other names

FabIEnoyl-ACP reductasetrans-2-enoyl-ACP reductase [NADH]NADH-dependent enoyl-ACP reductaseENR

FabI inhibitors bind to the enoyl-acyl carrier protein reductase enzyme, often forming a stable ternary complex with the NAD+ or NADH cofactor to prevent the reduction of the double bond in the fatty acid substrate, thereby disrupting the bacterial FAS-II pathway [1, 10, 22].