title: Cyclization of polyketides and non-ribosomal peptides on and off their assembly lines.
abstract: Modular polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are multifunctional megaenzymes that serve as templates to program the assembly of short carboxylic acids and amino acids in a primarily co-linear manner. The variation, combination, permutation and evolution of their functional units (e.g., modules, domains and proteins) along with their association with external enzymes have resulted in the generation of numerous versions of templates, the roles of which have not been fully recognized in the structural diversification of polyketides, non-ribosomal peptides and their hybrids present in nature. In this Highlight, we focus on the assembly-line enzymology and associated chemistry by providing examples of some newly characterized cyclization reactions that occur on and off the assembly lines during and after chain elongation for the purpose of elucidating the template effects of PKSs and NRPSs. A fundamental understanding of the underlying biosynthetic logic would facilitate the elucidation of chemical information contained within the PKS or NRPS templates and benefit the development of strategies for genome mining, biosynthesis-inspired chemical synthesis and combinatorial biosynthesis.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. wliu@mail.sioc.ac.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. wliu@mail.sioc.ac.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. wliu@mail.sioc.ac.cn and Huzhou Center of Bio-Synthetic Innovation, 1366 Hongfeng Road, Huzhou 313000, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
mesh_terms: D003500:Cyclization; D015394:Molecular Structure; D010453:Peptide Synthases / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D010455:Peptides; D061065:Polyketides; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase