Iterative polyketide biosynthesis by modular polyketide synthases in bacteria

• Published in: Applied microbiology and biotechnology 2016-01, Vol.100 (2), p.541-557
• Main Authors: Chen, Haotong, Du, Liangcheng
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analysis; Bacteria; Bacteria - enzymology; Bacteria - metabolism; Bacterial proteins; bioactive properties; Biological Products - metabolism; Biomedical and Life Sciences; Biosynthesis; Biosynthetic Pathways; Biotechnology; Carbon; Engineering; Health aspects; Life Sciences; Metabolites; Microbial Genetics and Genomics; Microbiology; Mini-Review; Natural products; Observations; Phylogenetics; polyketide synthases; Polyketide Synthases - metabolism; Polyketides; Polyketides - metabolism; Polypeptides; Secondary Metabolism; Studies; Substrate Specificity
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-015-7093-0

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.