ACPbinding

ACP-binding is the specific, often transient interaction between the acyl carrier protein (ACP) and partner enzymes or modules in fatty acid synthase II (FAS II) and related polyketide synthase (PKS) systems. ACP is a small, acidic protein that carries growing acyl chains via a 4'-phosphopantetheine prosthetic group attached to a conserved serine. The bound carrier and pantetheine arm position substrates within enzyme active sites, enabling sequential chain elongation and modification.

Within bacterial FAS II, ACP (AcpP in Escherichia coli) shuttles intermediates to dehydratases, reductases, and ketosynthases such as FabA, FabZ, FabG, FabI, FabF, and FabB. In PKS and other modular systems, ACP interacts with ketosynthases, ketoreductases, dehydratases, enoylreductases, and acyltransferases. These interactions are typically transient and modular, with ACP delivering a thioester-linked substrate to each catalytic site.

Structural and biophysical studies show ACP binding relies on complementary electrostatic surfaces and hydrophobic contacts, with conformational changes of the ACP pantetheine arm allowing docking across diverse partners. NMR, X-ray crystallography, and cross-linking have revealed features such as the four-helix ACP fold and flexible loops that regulate access to the thioester.

Maturation and regulation: ACP is synthesized as an apoprotein (apo-ACP) and converted to the active holo-ACP form by phosphopantetheinyl transferases (e.g., AcpS). Editing enzymes such as AcpH can remove the prosthetic group, modulating ACP availability. The ACP–enzyme interface can be targeted to alter biosynthesis or to develop antibiotics and engineer pathways for natural product production.

Advances in understanding ACP-binding inform antibiotic design, metabolic engineering, and synthetic biology. Techniques such as NMR spectroscopy, crystallography, and cross-linking mass spectrometry aid in mapping binding surfaces and dynamics.