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Iterative polyketide biosynthesis by modular polyketide synthases in bacteria

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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 isnon-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 thecanonical 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.

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Funding

This study was supported in part by the NIH (R01AI097260), NSFC (31329005), and a University of Nebraska-Lincoln Redox Biology Center pilot grant.

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  1. Department of Chemistry, University of Nebraska—Lincoln, Lincoln, NE, 68588, USA

    Haotong Chen & Liangcheng Du

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  1. Haotong Chen
  2. Liangcheng Du

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Correspondence toLiangcheng Du.

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Haotong Chen declares that she has no conflict of interest; Liangcheng Du declares that he has no conflict of interest.

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Chen, H., Du, L. Iterative polyketide biosynthesis by modular polyketide synthases in bacteria.Appl Microbiol Biotechnol100, 541–557 (2016). https://doi.org/10.1007/s00253-015-7093-0

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