Fatty acid synthase II enoyl-acyl carrier protein reductase (ENR)

Fatty acid synthase II enoyl-acyl carrier protein reductase (ENR) is a key enzyme of the type II fatty acid synthase system found in bacteria and plant plastids. It catalyzes the final reduction step of the elongation cycle: the conversion of trans-2-enoyl-ACP to fully saturated acyl-ACP using NADH or NADPH as a cofactor. In bacteria such as Escherichia coli, the canonical ENR is encoded by the fabI gene, but alternative isoforms (FabK, FabV, FabL) exist in other species. ENR is essential for membrane phospholipid biosynthesis and is a validated antimicrobial target since inhibiting this enzyme leads to depletion of fatty acids, membrane failure, and loss of viability in susceptible organisms[7][6][2][5][4]. Several clinically relevant drugs, such as triclosan and isoniazid, act by inhibiting ENR, and resistance can arise through gene mutations or acquisition of alternate isoforms. ENR is absent from human cytosolic fatty acid synthesis but is present in mitochondrial FAS, making bacterial ENR selective as a drug target[2][6].

Other names

Enoyl-acyl carrier protein reductaseEnoyl-ACP reductaseENRFabI (Escherichia coli and many gram-negative bacteria)FabK, FabL, FabV (other bacterial ENR isoforms)NADH-dependent enoyl-ACP reductase

Competitive inhibition of the NADH/NADPH binding site - Inhibition of enoyl-ACP substrate binding - Disruption of fatty acid elongation by preventing final reduction in the cycle