3hydroxyacylACP

3-hydroxyacyl-ACP is an acyl carrier protein (ACP)–bound intermediate in the bacterial and plant plastid type II fatty acid synthase (FAS II) system. The growing acyl chain is tethered to the ACP via a 4'-phosphopantetheine prosthetic group, which allows the chain to be positioned for successive enzymatic steps without diffusing freely in solution.

Formation and role in fatty acid synthesis

In the FAS II cycle, the condensation of a growing acyl-ACP with malonyl-ACP forms a β-ketoacyl-ACP. This intermediate is then reduced by β-ketoacyl-ACP reductase (FabG) using NADPH to yield 3-hydroxyacyl-ACP, with the hydroxy group located on the beta carbon. The 3-hydroxyacyl-ACP serves as a key branching point for the cycle: it is dehydrated by a dehydratase (FabA or FabZ) to form an enoyl-ACP, which is subsequently reduced by enoyl-ACP reductase (FabI) to extend the growing acyl chain by two carbons. Repetition of these steps leads to progressively longer saturated acyl-ACPs, such as palmitoyl-ACP, which can then be transferred to other pathways or used in membrane lipid synthesis.

Enzymatic context and diversity

The β-ketoacyl-ACP reductase FabG is NADPH-dependent and is one of several discrete enzymes in the bacterial FAS II system, allowing parallel specialization of functions compared with the single multi-domain type I FAS found in animals. The sequence of reactions around 3-hydroxyacyl-ACP is conserved in many bacteria and plant plastids, though variations exist in enzyme families and regulation across organisms.

Importance

3-hydroxyacyl-ACP is essential for the proper elongation cycle of fatty acid synthesis in organisms relying on the FAS II system. Its correct formation and timely conversion influence both fatty acid chain length distribution and membrane lipid composition.