Holo-[acyl-carrier-protein] synthase (ACPS) (ACPS)

Holo-[acyl-carrier-protein] synthase (ACPS) is an essential enzyme in bacteria that plays a pivotal role in the fatty acid synthesis (FAS II) pathway (UniProt P0A6G5; Wikipedia). It is responsible for the post-translational activation of the apo-acyl carrier protein (apo-ACP) by transferring a 4'-phosphopantetheinyl group from Coenzyme A to a specific serine residue on the ACP (Lambalot et al., 1996, PMID: 8849441). This modification converts the inactive apo-protein into the functional holo-ACP, which is required for the transport of acyl intermediates during the assembly of fatty acids, polyketides, and non-ribosomal peptides (Chirgadze et al., 2000, PMID: 10835001). Since fatty acids are crucial for the integrity of the bacterial cell wall and membrane, ACPS is vital for bacterial survival and growth (McAllister et al., 2006, PMID: 16433571). Given its essentiality and the structural differences between bacterial ACPS and human phosphopantetheinyl transferases, it has emerged as a significant target for the development of new classes of antibiotics (Zheng et al., 2005, PMID: 15653343). Inhibiting this enzyme effectively halts primary metabolism, making it a potent focus for treating multi-drug resistant bacterial infections.

Other names

Acyl carrier protein synthaseAcpS4'-phosphopantetheinyl transferasePPTaseHolo-ACP synthaseTransferase (phosphopantetheinyl)

Inhibition of the transfer of the 4'-phosphopantetheinyl moiety from Coenzyme A to apo-acyl carrier protein, preventing the formation of active holo-acyl carrier protein and disrupting fatty acid biosynthesis.