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

Staphylococcal enoyl-acyl carrier protein reductase (FabI) is a critical enzyme in the bacterial Type II fatty acid synthesis (FAS II) pathway, particularly in Staphylococcus aureus and other staphylococci (1.1.1, 1.5.1). It catalyzes the final, rate-limiting reduction step in the fatty acid elongation cycle, converting trans-2-enoyl-ACP to acyl-ACP using NADPH as a cofactor (1.3.3, 1.5.4). This enzyme is essential for the production of membrane lipids and overall bacterial viability (1.1.2, 1.2.1). Because the FAS II pathway is structurally and organizationally distinct from the human Type I fatty acid synthase (FAS I), FabI serves as a highly selective target for novel antibiotics (1.1.4, 1.3.2). Drugs such as afabicin (Debio 1450) specifically inhibit this enzyme, leading to the depletion of essential fatty acids and subsequent bacterial cell death (1.2.1, 1.2.5). This target is especially valuable for treating multidrug-resistant infections, such as methicillin-resistant S. aureus (MRSA), while minimizing disruption to the host's commensal microbiota due to its narrow-spectrum activity (1.2.1, 1.4.1). Resistance can emerge through mutations in the fabI gene, which is a key consideration in drug development (1.1.2, 1.4.2). Clinical trials have demonstrated the efficacy of FabI inhibitors in treating skin and bone infections (1.2.1, 1.2.5).

Other names

Enoyl-ACP reductaseENRsaFabINADPH-dependent enoyl-ACP reductaseStaphylococcal enoyl-acyl carrier protein reductase

Inhibition of the final reduction step in the fatty acid elongation cycle, specifically the reduction of trans-2-enoyl-ACP to acyl-ACP, which disrupts the Type II fatty acid synthesis (FAS II) pathway.