Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

Dinesh Simkhada, Huitu Zhang, Shogo Mori, Howard Williams, Coran M.H. Watanabe

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

At least 65% of all small molecule drugs on the market today are natural products, however, re-isolation of previously identified and characterized compounds has become a serious impediment to the discovery of new bioactive natural products. Here, genetic knockout of an unusual non-ribosomal peptide synthetase (NRPS) C-PCP-C module, aziA2, is performed resulting in the accumulation of the secondary metabolite, dimethyl furan-2,4-dicarboxylate. The cryptic metabolite represents the first non-azinomycin related compound to be isolated and characterized from the soil bacterium, S. sahachiroi. The results from this study suggest that abolishing production of otherwise predominant natural products through genetic knockout may constitute a means to "activate" the production of novel secondary metabolites that would otherwise lay dormant within microbial genome sequences.

Original languageEnglish (US)
Pages (from-to)1768-1773
Number of pages6
JournalBeilstein Journal of Organic Chemistry
Volume9
DOIs
StatePublished - Aug 29 2013
Externally publishedYes

Keywords

  • Cryptic metabolite
  • Dimethyl furan-2,4-dicarboxylate
  • Genetic knockout
  • Natural products
  • Non-ribosomal peptide synthetase module
  • Streptomyces

ASJC Scopus subject areas

  • Organic Chemistry

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