The acyl carrier protein (ACP) is an important component in both fatty acid and
polyketide biosynthesis with the growing chain bound during synthesis as a thiol ester at the
distal thiol of a 4'-phophopantethiene moiety. The protein is expressed in the inactive apo form and the
4'-phosphopantetheine moiety must be post-translationally attached to a conserved serine residue on the ACP by the action of
holo-acyl carrier protein synthase (ACPS) a phosphopantetheinyl
transferase.
4'-Phosphopantetheine is an essential prosthetic group of several acyl carrier
proteins involved in pathways of primary and secondary metabolism including the acyl carrier proteins (ACP) of fatty acid
synthases, ACP of polyketide synthases, and peptidyl carrier proteins (PCP) and aryl carrier proteins (ArCP) of nonribosomal peptide synthetases (NRPS). Phosphopantetheine fulfils two demands in these biosynthetic
pathways. Firstly, the intermediates remain covalently linked to the synthases (or synthetases) in an energy-rich linkage.
Secondly, the flexibility and length of phosphopantetheine chain (approximately 2 nm) allows the covalently tethered
intermediates to have access to spatially distinct enzyme active sites. This increases the effective molarity of the intermediate
and allows an assembly line like process.
Structurally, the ACPs are small negatively charged α-helical bundle proteins with a high degree of structural and amino acid
similarity. The structures of a number of acyl carrier proteins have been solved using various NMR and crystallography techniques.
The ACP's are structural and mechanistically related to the peptidyl carrier proteins (PCP) from nonribosomal peptide synthases.
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