EnoylACP

Enoyl-ACP refers to the acyl carrier protein-bound enoyl group that appears as an intermediate during fatty acid synthesis in many bacteria and plant plastids. In the type II fatty acid synthase (FAS II) system, growing acyl chains are attached to an acyl carrier protein (ACP) via a phosphopantetheine thioester. Through a cycle of condensation, reduction, dehydration, andReduction, two-carbon units are added to the growing chain, generating a beta-hydroxyacyl-ACP, which is dehydrated to form an enoyl-ACP, most commonly a trans-2-enoyl-ACP. This enoyl-ACP is then reduced by enoyl-ACP reductase to produce a longer saturated acyl-ACP, continuing the elongation cycle.

Distribution and enzymes: Enoyl-ACP intermediates occur in bacteria and plant plastids that utilize FAS II pathways. The dehydration step is typically carried out by dehydratases such as FabA or FabZ, producing enoyl-ACP. The subsequent reduction is carried out by enoyl-ACP reductases, with different organisms employing FabI, FabK, FabL, or FabV variants. Variability in reductases can influence sensitivity to inhibitors and antibiotics.

Chemical nature and role: The enoyl-ACP intermediate is a thioester-linked, unsaturated (usually trans-2) acyl-ACP. Its formation marks a key branching point in the elongation cycle, directing the molecule toward further two-carbon additions and eventual production of longer fatty acids or specialized lipids.

Clinical significance: Enoyl-ACP reductases are targets for antibiotic and antimicrobial agents. Inhibitors of FabI and related enzymes can disrupt bacterial fatty acid biosynthesis, highlighting enoyl-ACP–related steps as potential drug targets.