hydroxyacylACP

Hydroxyacyl-ACP refers to acyl carrier protein-bound beta-hydroxyacyl thioesters that arise as intermediates during fatty acid biosynthesis in type II fatty acid synthase (FAS II) systems, found in many bacteria and in the plastids of plant cells. The most common form is 3-hydroxyacyl-ACP, in which a hydroxyl group is situated at the beta position of the growing acyl chain attached to the ACP via a phosphopantetheine arm.

In FAS II, the growing acyl chain is carried by ACP. Condensation with malonyl-ACP by beta-ketoacyl-ACP synthase forms beta-ketoacyl-ACP, which is reduced by beta-ketoacyl-ACP reductase FabG to 3-hydroxyacyl-ACP. This intermediate is dehydrated by beta-hydroxyacyl-ACP dehydratase (FabA or FabZ) to an enoyl-ACP, which is reduced by enoyl-ACP reductase (FabI) to a longer acyl-ACP, continuing the cycle. The hydroxyacyl-ACP intermediates are typically short-lived and are further processed until the fatty acid reaches its final length, after which a thioesterase releases the mature fatty acid.

Occurrence and significance: Hydroxyacyl-ACP intermediates are central to the iterative elongation steps of fatty acid biosynthesis in organisms employing FAS II. Their proper processing is essential for efficient fatty acid production. Because several enzymes in the pathway are essential and distinct from mammalian FAS systems, components of the hydroxyacyl-ACP pathway are targets for antibacterial agents that disrupt bacterial fatty acid synthesis.