title: Iterative polyketide biosynthesis by modular polyketide synthases in bacteria.
abstract: Modular polyketide synthases (type I PKSs) in bacteria are responsible for synthesizing a significant percentage of bioactive natural products. This group of synthases has a characteristic modular organization, and each module within a PKS carries out one cycle of polyketide chain elongation; thus each module is non-iterative in function. It was possible to predict the basic structure of a polyketide product from the module organization of the PKSs, since there generally existed a co-linearity between the number of modules and the number of chain elongations. However, more and more bacterial modular PKSs fail to conform to the canonical rules, and a particularly noteworthy group of non-canonical PKSs is the bacterial iterative type I PKSs. This review covers recent examples of iteratively used modular PKSs in bacteria. These non-canonical PKSs give rise to a large array of natural products with impressive structural diversity. The molecular mechanism behind the iterations is often unclear, presenting a new challenge to the rational engineering of these PKSs with the goal of generating new natural products. Structural elucidation of these synthase complexes and better understanding of potential PKS-PKS interactions as well as PKS-substrate recognition may provide new prospects and inspirations for the discovery and engineering of new bioactive polyketides.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.
authors.forename: Haotong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA. ldu3@unl.edu.
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Du
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology / Q000378:metabolism*; D001688:Biological Products / Q000378:metabolism; D053898:Biosynthetic Pathways; D048630:Polyketide Synthases / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism*; D064210:Secondary Metabolism; D013379:Substrate Specificity
chemical_list: D001688:Biological Products; D061065:Polyketides; D048630:Polyketide Synthases
keywords: Biosynthesis; Iterative PKS; Natural products; Polyketides; Type I PKS