Structure elucidation of colibactin and its DNA cross-links-Reference-Cited by-同舟云学术

Structure elucidation of colibactin and its DNA cross-links

Published:2019-09-06 Issue:6457 Volume:365 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Xue Mengzhao¹^ORCID,Kim Chung Sub¹²^ORCID,Healy Alan R.¹²^ORCID,Wernke Kevin M.¹^ORCID,Wang Zhixun¹^ORCID,Frischling Madeline C.¹^ORCID,Shine Emilee E.²³^ORCID,Wang Weiwei⁴⁵^ORCID,Herzon Seth B.¹⁶^ORCID,Crawford Jason M.¹²³^ORCID

Affiliation:

1. Department of Chemistry, Yale University, New Haven, CT 06520, USA.

2. Chemical Biology Institute, Yale University, West Haven, CT 06516, USA.

3. Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536, USA.

4. Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT 06520, USA.

5. W. M. Keck Biotechnology Resource Laboratory, Yale School of Medicine, New Haven, CT 06510, USA.

6. Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA.

Abstract

Double warhead does DNA damage Strains of the human gut bacterium Escherichia coli carrying the clb 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 et al. 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. Science , this issue p. eaax2685

Funder

National Science Foundation

National Institutes of Health

Charles H. Revson Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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