Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

Sharma, Sunil V., Tong, Xiaoxue, Pubill-Ulldemolins, Cristina, Cartmell, Christopher, Bogosyan, Emma J. A., Rackham, Emma J., Marelli, Enrico, Hamed, Refaat B. and Goss, Rebecca J. M. (2017) Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo. Nature Communications, 8. ISSN 2041-1723

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Abstract

Marrying synthetic biology with synthetic chemistry provides a powerful approach toward natural product diversification, combining the best of both worlds: expediency and synthetic capability of biogenic pathways and chemical diversity enabled by organic synthesis. Biosynthetic pathway engineering can be employed to insert a chemically orthogonal tag into a complex natural scaffold affording the possibility of site-selective modification without employing protecting group strategies. Here we show that, by installing a sufficiently reactive handle (e.g., a C–Br bond) and developing compatible mild aqueous chemistries, synchronous biosynthesis of the tagged metabolite and its subsequent chemical modification in living culture can be achieved. This approach can potentially enable many new applications: for example, assay of directed evolution of enzymes catalyzing halo-metabolite biosynthesis in living cells or generating and following the fate of tagged metabolites and biomolecules in living systems. We report synthetic biological access to new-to-nature bromo-metabolites and the concomitant biorthogonal cross-coupling of halo-metabolites in living cultures.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Chemistry
Faculty of Science > School of Chemical Sciences and Pharmacy
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Depositing User: Pure Connector
Date Deposited: 18 Aug 2017 05:06
Last Modified: 19 Sep 2019 00:25
URI: https://ueaeprints.uea.ac.uk/id/eprint/64567
DOI: 10.1038/s41467-017-00194-3

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