Holo-acyl carrier protein synthase (AcpS)

Holo-acyl carrier protein synthase (AcpS) is an essential enzyme in bacteria and certain parasites responsible for the post-translational activation of acyl carrier proteins (ACPs) [UniProt: P0A6G5]. It catalyzes the transfer of the 4'-phosphopantetheinyl moiety from Coenzyme A to a specific serine residue on the apo-ACP, converting it into the functional holo-ACP [PubMed: 12678620]. This activation is essential for the biosynthesis of fatty acids, polyketides, and non-ribosomal peptides, which are critical for cell membrane integrity and secondary metabolite production [PubMed: 15103634]. Because AcpS is indispensable for bacterial survival and differs significantly from human phosphopantetheinyl transferases, it is a highly attractive target for the development of novel narrow-spectrum and broad-spectrum antibiotics [PubMed: 11585362]. Inhibitors of AcpS, such as Sch-538415, disrupt these essential metabolic pathways, leading to bacterial growth inhibition or death, making it a focus for treating multi-drug resistant infections [PubChem: CID 10442544]. Research into AcpS inhibitors aims to address the global challenge of antibiotic resistance by targeting a pathway distinct from those affected by current clinical drugs. The enzyme's structural conservation across many pathogenic species further enhances its potential as a broad-spectrum antimicrobial target.

Other names

4'-phosphopantetheinyl transferaseAcpSHolo-ACP synthasePhosphopantetheinyl transferasePPTase

Inhibition of the transfer of the 4'-phosphopantetheinyl moiety from Coenzyme A to apo-acyl carrier protein (apo-ACP), thereby preventing the formation of the active holo-ACP required for fatty acid and secondary metabolite biosynthesis.