Iterative polyketide biosynthesis by modular polyketide synthases in bacteria

Haotong Chen, Liangcheng Du

Research output: Contribution to journalReview article

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)541-557
Number of pages17
JournalApplied Microbiology and Biotechnology
Volume100
Issue number2
DOIs
StatePublished - Jan 1 2016

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Keywords

  • Biosynthesis
  • Iterative PKS
  • Natural products
  • Polyketides
  • Type I PKS

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

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