Hybrid Peptide-Polyketide Natural Products: Biosynthesis and Prospects Towards Engineering Novel Molecules

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Polyketides and nonribosomal peptides are two groups of secondary metabolites found in many microorganisms and plants. Biosynthesis and genetic engineering of polyketide and nonribosomal peptide natural products are active areas in both academia and industry. The current renaissance of the field is driven by: (a) the unparallel biological activities and enormous commercial value of these natural products, the use of which remains to be the single most successful strategy for new drug discovery; (b) the extraordinary structure, mechanism, and catalytic reactivity of the polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) that provide an unprecedented opportunity to investigate the molecular mechanism of enzyme catalysis, molecular recognition and protein-protein interaction; and (c) the remarkable versatility and amenability of their biosynthetic machineries via combinatorial biosynthesis that allow the generation of novel compounds and chemical structural diversity that are difficult to access by other means (13).