PRECURSOR-DIRECTED BIOSYNTHESIS OF POLYKETIDE AND NONRIBOSOMAL PEPTIDE NATURAL PRODUCTS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 483

FIGURE 14.1 Schematic overview of polyketide biosynthesis.

(A domain) selects the extender unit, in this case an amino acid, and activates it for
coupling using ATP to form an adenylate. The A domain then transfers the activated
amino acid to the NRPS equivalent of PKSACP, the peptidyl carrier protein (PCP). As
the initiation module PCP is charged with an amino acid, an analogous process takes
place with the A and PCP domains of module 1. Once adenylated amino acids are
present on both the initiation module and the module 1, formation of the first peptide
bond is catalyzed by the condensation domain (C domain). This canonical domain
within the NRPS is the equivalent of the KS domain of the PKS. The resulting
dipeptide that is covalently tethered to the PCP of module 1 serves as the electrophile
in the subsequent condensation reaction. Each condensation occurs in an analogous
fashion, with the nascent peptide growing by a single amino acid at each module.
When the full-length peptide chain is formed, a thioesterase cleaves the product from
the final PCP domain, in many cases catalyzing the cyclization of the peptide product.