Abstract
Colibactin is an as-yet-uncharacterized genotoxic secondary metabolite produced by human gut bacteria. Here we report the biosynthetic discovery of two new precolibactin molecules from Escherichia coli, including precolibactin-886, which uniquely incorporates the highly sought genotoxicity-associated aminomalonate building block into its unprecedented macrocyclic structure. This work provides new insights into the biosynthetic logic and mode of action of this colorectal-cancer-linked microbial chemical.
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Acknowledgements
This work was generously supported by grants from the China Ocean Mineral Resources Research and Development Association (13.5 program to P.-Y.Q.) and the NIH (R01-GM85770 to B.S.M.). We thank P.R. Jensen, J. Busch, C.B. Naman, and Y.K. Tam for technical advice and access to equipment.
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Z.-R.L., J.L., J.-P.G., J.Y.H.L., B.M.D., W.-P.Z., Z.-L.L., Y.-X.L., R.-B.T., Y.X., and D.-H.L. performed experiments and collected data; all authors analyzed data; Z.-R.L., J.L., B.S.M., and P.-Y.Q. designed the study and wrote the manuscript.
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Li, ZR., Li, J., Gu, JP. et al. Divergent biosynthesis yields a cytotoxic aminomalonate-containing precolibactin. Nat Chem Biol 12, 773–775 (2016). https://doi.org/10.1038/nchembio.2157
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DOI: https://doi.org/10.1038/nchembio.2157
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