Cited by 257Microbial Natural Products and BiosynthesisMicrobial Metabolism and ApplicationsBioactive Compounds and Antitumor Agents

Structure Elucidation of Colibactin and Its DNA Cross-Links

Open access
Xue, Mengzhao, Kim, Chung Sub, Healy, Alan R., Wernke, Kevin M., Wang, Zhixun, Frischling, Madeline C., Shine, Emilee E., Wang, Weiwei +2 more·2019·Science

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

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  • Metabolites produced by some intestinal microbiota may be genotoxic and can directly induce DNA damage of host cells or modulate host cell signaling pathways involved in cell proliferation and apoptosis.

    “Metabolites produced by some intestinal microbiota may be genotoxic and can directly induce DNA damage of host cells or modulate the basic host cell signaling pathways involved in cell proliferation and apoptosis.”

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  1. [43]Bell RP, in Advances in Physical Organic Chemistry, Gold V, Ed. (Academic Press, 1966), vol. 4, pp. 1– 29.

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Authors
Xue, M., Kim, C. S., Healy, A. R., Wernke, K. M., Wang, Z., Frischling, M. C., Shine, E. E., Wang, W., Herzon, S. B., & Crawford, J. M.
Affiliations
Yale University (US)
Corresponding author
  • Xue, Mengzhao
  • Kim, Chung Sub
  • Herzon, Seth B.
  • Crawford, Jason M.
Venue
Science
Published
2019-09-06
Volume
365
Issue
6457
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2967933500
Cited by
257
References
47
Citations by year
2026: 24 · 2025: 42 · 2024: 40 · 2023: 26 · 2022: 38 · 2021: 43 · 2020: 34 · 2019: 10
FWCI
19.37
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health (R01GM110506, 1DP2-CA186575, R01CA215553, T32GM067543)
  • Charles H. Revson Foundation
Topics
  • Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Metabolism and Applications
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Keywords
colibactin, DNA cross-links, structure elucidation, colorectal cancer, gut microbiota, bacterial virulence factors, isotopic labeling, tandem mass spectrometry, chemical synthesis
MeSH terms
Escherichia coli, Isotope Labeling, Mutation, Peptide Hydrolases, Peptides, Protein Conformation, DNA Adducts, Escherichia coli Proteins, Tandem Mass Spectrometry, Polyketides, Secondary Metabolism

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