malonylACP

Malonyl-ACP is the thioester formed when the malonyl group is attached to the phosphopantetheine prosthetic group of an acyl carrier protein (ACP) involved in fatty acid biosynthesis. In organisms that employ the type II fatty acid synthase (FAS II) system, malonyl-ACP acts as the two-carbon donor required for iterative chain elongation.

Biosynthesis and transfer occur in two main steps. First, acetyl-CoA is carboxylated by acetyl-CoA carboxylase to form malonyl-CoA. Second, the malonyl group is transferred from malonyl-CoA to ACP by the malonyl-CoA:ACP transacylase (FabD), yielding malonyl-ACP. The ACP contains a 4'-phosphopantetheine prosthetic arm that tethers the growing and donor acyl groups as thioesters, enabling shuttling between catalytic centers.

Role in chain elongation is mediated by condensing enzymes. β-Ketoacyl-ACP synthases (FabF and FabB) catalyze the decarboxylative condensation of malonyl-ACP with a primed acyl-ACP, releasing CO2 and forming a longer β-ketoacyl-ACP. This β-keto intermediate is then modified through reduction, dehydration, and another reduction to extend the fatty acyl chain, with successive cycles using additional malonyl-ACP units.

Structure and function of ACP are key to its role. ACP is a small, acidic protein (~9–10 kDa) whose serine residue hosts the 4'-phosphopantetheine arm; the malonyl moiety is bound as a thioester on this arm. This modular design allows precise substrate delivery and coordination among FAS II enzymes, making malonyl-ACP essential for bacterial and plant fatty acid biosynthesis.

Disruptions in malonyl-ACP formation or utilization can impede fatty acid production, placing components of this pathway as potential targets in antibiotic development.