Structure elucidation of colibactin and its DNA cross-links

  • Mengzhao Xue
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Chung Sub Kim
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Alan R. Healy
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Kevin M. Wernke
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Zhixun Wang
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Madeline C. Frischling
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Emilee E. Shine
    Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.
  • Weiwei Wang
    Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.
  • Seth B. Herzon
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Jason M. Crawford
    Department of Chemistry, Yale University, New Haven, CT 06520, USA.

書誌事項

公開日
2019-09-06
DOI
  • 10.1126/science.aax2685
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:title>Double warhead does DNA damage</jats:title> <jats:p> Strains of the human gut bacterium <jats:italic>Escherichia coli</jats:italic> carrying the <jats:italic>clb</jats:italic> gene cluster produce a secondary metabolite dubbed colibactin and have been provocatively linked to colorectal cancer in some models. Colibactin has been difficult to isolate in full, but pieces of the structure have been worked out, including an electrophilic warhead. Xue <jats:italic>et al.</jats:italic> found that colibactin contains two conjoined warheads, which is consistent with its ability to alkylate and cross-link DNA. Chemical synthesis and comparison to cell coculture confirm the structure and properties of this unstable and potentially carcinogenic metabolite. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.aax2685">eaax2685</jats:related-article> </jats:p>

収録刊行物

  • Science

    Science 365 (6457), 365-, 2019-09-06

    American Association for the Advancement of Science (AAAS)

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