Non-ribosomal peptide synthase NRPS

Fig. 5.2 Organization of polyketide synthases (PKSs). (A) The type I erythromycin PKS (DEBS) which catalyzes the biosynthesis of 6-dEB. The PKS consists of three polypeptides, DEBSl, DEBS2, and DEBS3, each possessing two modules. (B) The type I epothilone PKS consists of six polypeptides EpoA, EpoB [a non-ribosomal peptide synthase (NRPS)], EpoC, EpoD (possessing four modules), EpoE (possessing two modules), and EpoF. (C) The type II actinorhodin PKS con-...

An enormous range of medically important polyketide and peptide natural products assembled by modular polyketide synthases (PKSs), non-ribosomal peptide synthases (NRPSs) and mixed PKS/NRPS systems have macrocyclic structures, including the antibiotics erythromycin (PKS) and daptomycin (NRPS), the immunosuppressants cyclosporin (NRPS) and rapamycin (PKS/NRPS), and the antitumor agent epothilone (PKS/NRPS). PKSs and NRPSs are large, multifunctional proteins that are organized into sets of fnnc-tional domains termed modules. The order of modules corresponds directly to the seqnence of monomers in the product. Synthetic intermediates are covalently tethered by thioester linkages to a carrier protein domain in each module. The thiol tether on each carrier domain is phosphopantetheine, which is attached to a conserved serine residne in the carrier protein in a post-translational priming reaction catalyzed by a phosphopantetheinyltransferase. 

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