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Macrocyclic colibactins

Nature Chemistry volume 12, pages 1005–1006 (2020)Cite this article

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Matters Arising to this article was published on 21 September 2020

The Original Article was published on 16 September 2019

arising from Z.-R. Li et al. Nature Chemistry https://doi.org/10.1038/s41557-019-0317-7 (2019)

The carcinogenic mechanism of the bacteria is likely related to their ability to produce a molecule — colibactin — that induces DNA double-strand breaks3 and interstrand crosslinks4 in eukaryotic genomic DNA. The biosynthesis of colibactin is encoded in the clb (or pks) biosynthetic gene cluster3. Studies indicate all 16 biosynthetic enzymes in the gene cluster are required to produce the colibactin genotoxin linked to the disease3. Using well-established assays5 Li et al. showed that in the presence of a copper(ii) co-factor, both precolibactin-969 (1) and colibactin-645 (2) induce DNA single-strand breaks and double-strand breaks in DNA. DNA double-strand break repair was activated in HeLa cells treated with colibactin-645 (2), but not precolibactin-969 (1). Li et al. write ‘Precolibactin-969… requires all the components of the… assembly line for its biosynthesis’, suggesting they have identified the complete product of the clb biosynthetic gene cluster, namely, colibactin. However, this conclusion is called into question by the literature outlined below.

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Fig. 1: Structures of precolibactin-969 (1), colibactin-645 (2) and other structures discussed in this manuscript.

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Acknowledgements

Financial support from the National Institutes of Health (R01CA215553) is gratefully acknowledged.

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

    Seth B. Herzon

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

    Seth B. Herzon

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S.B.H. wrote the manuscript.

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Correspondence to Seth B. Herzon.

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Herzon, S.B. Macrocyclic colibactins. Nat. Chem. 12, 1005–1006 (2020). https://doi.org/10.1038/s41557-020-00551-8

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