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The mysteries of macrocyclic colibactins
Nature Chemistry, 2019The biosynthetic pathway that produces the structurally uncharacterized gut bacterial genotoxin colibactin can produce unstable, macrocyclic products; however, the extent to which these structures contribute to colibactin’s biological activities is not yet fully understood.
Erik S. Carlson, Emily P. Balskus
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Critical Intermediates Reveal New Biosynthetic Events in the Enigmatic Colibactin Pathway
ChemBioChem, 2015 Colibactin is a potent genotoxin that induces DNA double-strand breaks; it is produced by Escherichia coli strains harboring a pks+ island. However, the structure of this compound remains elusive. Here, using transformation-associated recombination (TAR)
Guoqiang Zhu +2 more
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Journal of the American Chemical Society, 2021
Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing Escherichia coli has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis.
Tao Zhou +15 more
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Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing Escherichia coli has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis.
Tao Zhou +15 more
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Carriage of Colibactin-producing Bacteria and Colorectal Cancer Risk
Trends in Microbiology, 2020Colibactin is a genotoxic molecule, produced primarily by Escherichia coli. Colibactin causes DNA damage that may lead to colorectal cancer. Here we review recent advances in the study of colibactin and propose a focus on patients with inflammatory bowel diseases (IBD) who have higher levels of colibactin-producing bacteria in their intestines.
Vadim Dubinsky, Iris Dotan, Uri Gophna
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Closing in on the elusive colibactin toxin
C&EN Global Enterprise, 2019More than a decade ago, researchers discovered that bacteria in the human gut have been organizing a mutiny. They produce a toxin capable of damaging our DNA. The team, led by Eric Oswald and Jean-Philippe Nougayrede of Inserm, a French medical research institute, reported that strains of Escherichia coli containing a particular gene cluster could ...
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Researchers elucidate colibactin structure
C&EN Global Enterprise, 2019Some Escherichia coli bacteria in the gut produce a family of metabolites called colibactins, which are associated with increased risk of colon cancer in people.
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A Prodrug Resistance Mechanism Is Involved in Colibactin Biosynthesis and Cytotoxicity
Journal of the American Chemical Society, 2013Commensal Escherichia coli residing in the human gut produce colibactin, a small-molecule genotoxin of unknown structure that has been implicated in the development of colon cancer. Colibactin biosynthesis is hypothesized to involve a prodrug resistance strategy that entails initiation of biosynthesis via construction of an N-terminal prodrug scaffold ...
Carolyn A, Brotherton, Emily P, Balskus
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Colibactin: understanding an elusive gut bacterial genotoxin
Natural Product Reports, 2015This highlight reviews recent studies of colibactin, a structurally uncharacterized genotoxin synthesized by members of the human gut microbiota.
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Microbiota and colorectal cancer: colibactin makes its mark
Nature Reviews Gastroenterology & Hepatology, 2020Colibactin-producing bacteria are abundant in the gut microbiota of colorectal cancer tumours and promote colon tumorigenesis in mouse models. Now, a new study demonstrates a direct link between exposure of human intestinal epithelial cells to colibactin and two unique mutational fingerprints found in human colorectal tumours.
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