ArticleNature chemistry2019
Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.
- The current status and prospects of gut microbiota combined with PD-1/PD-L1 inhibitors in the treatment of colorectal cancer: a review.BMC gastroenterology · 2025Pooled it
- Intratumoral microbiota composition in women's cancers: a systematic review and meta-analysis.Frontiers in oncology · 2025Pooled it
- Development of an efficient genome editing system using recombinase-mediated cassette exchange inSynthetic and systems biotechnology · 2026Article
- Apurinic/apyrimidinic endonuclease 1 prevents oxidative DNA damage in intestinal epithelial cells induced by genotoxic Escherichia coli NC101.Redox biology · 2026Article
- Review
- Cellular effects of outer membrane vesicles isolated from pks-positive strains of bacteria.Research square · 2026Article
- Genomic Map of Escherichia coli and Single Nucleotide Polymorphism Markers in Colorectal Cancer.Microbial biotechnology · 2026Article
- Analysis of intratumoural bacteria: Opportunities and challenges for cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Homoisoflavanone Delays Colorectal Cancer Progression via DNA Damage-Induced Mitochondrial Apoptosis and Parthanatos-Like Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Intratumoral microbiota: implications for colorectal cancer pathogenesis and therapy.Frontiers in immunology · 2026Review
- Research advances on the urinary microbiome in non-infectious urinary tract diseases: from community composition to clinical prospects.Frontiers in cellular and infection microbiology · 2026Review
- Role of Gut Microbiome in Oncogenesis and Oncotherapies.Cancers · 2025Review
- The specificity and structure of DNA cross-linking by the gut bacterial genotoxin colibactin.Science (New York, N.Y.) · 2025Article
- The specificity and structure of DNA crosslinking by the gut bacterial genotoxin colibactin.bioRxiv : the preprint server for biology · 2025Article
- Leveraging chemical synthesis to discover metabolites from the gut microbiome.Annals of the New York Academy of Sciences · 2025Review
- Synergistic action of specialized metabolites from divergent biosynthesis in the human oral microbiome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Gut Escherichia coli promotes lung cancer by increasing circulating STAMBP production.Discover oncology · 2025Article
- Bacterial small molecule metabolites implicated in gastrointestinal cancer development.Nature reviews. Microbiology · 2025Review
- The intratumor microbiota and thyroid cancer: a review.Frontiers in endocrinology · 2025Review
- Article
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9 authors at 3 institutions in 2 countries.
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Abstract
Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.