Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: Logic, machinery, and mechanisms

Evidence suggests that polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes are organized in clusters. This basic knowledge of PKS and NRPS systems provides context for more efficient efforts in combinatorial biosynthesis to create collections of natural product variants with novel structure and function. In view of this information, an overview is given of the logic of assembly-line enzymology, enzyme machinery, assembly-line operations and mechanisms of PKS and NRPS assembly.