Unraveling the iterative type I polyketide synthases hidden in Streptomyces

Bin Wang, Fang Guo, Chunshuai Huang, Huimin Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

Type I polyketide synthases (T1PKSs) are one of the most extensively studied PKSs, which can act either iteratively or via an assembly-line mechanism. Domains in the T1PKSs can readily be predicted by computational tools based on their highly conserved sequences. However, to distinguish between iterative and noniterative at the module level remains an overwhelming challenge, which may account for the seemingly biased distribution of T1PKSs in fungi and bacteria: small iterative monomodular T1PKSs that are responsible for the enormously diverse fungal natural products exist almost exclusively in fungi. Here we report the discovery of iterative T1PKSs that are unexpectedly both abundant and widespread in Streptomyces Seven of 11 systematically selected T1PKS monomodules from monomodular T1PKS biosynthetic gene clusters (BGCs) were experimentally confirmed to be iteratively acting, synthesizing diverse branched/nonbranched linear intermediates, and two of them produced bioactive allenic polyketides and citreodiols as end products, respectively. This study indicates the huge potential of iterative T1PKS BGCs from streptomycetes in the discovery of novel polyketides.

Original languageEnglish (US)
Pages (from-to)8449-8454
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number15
DOIs
StatePublished - Apr 14 2020

Keywords

  • biosynthetic gene clusters
  • iterative
  • natural product discovery
  • polyketide synthase

ASJC Scopus subject areas

  • General

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