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    Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

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    Publication date
    2017-08-09
    Author
    Sharma, S.V.
    Tong, X.
    Pubill-Ulldemolins, C.
    Cartmell, C.
    Bogosyan, E.J.A.
    Rackham, E.J.
    Marelli, E.
    Hamed, Refaat B.
    Goss, R.J.M.
    Keyword
    GenoChemetics
    Synthetic biology
    Synthetic chemistry
    Biogenic pathways
    Organic synthesis
    Rights
    (c) 2017 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/)
    Peer-Reviewed
    Yes
    
    Metadata
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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.
    URI
    http://hdl.handle.net/10454/17009
    Version
    Accepted manuscript
    Citation
    Sharma SV, Tong X, Pubill-Ulldemolins C et al (2017) Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo. Nature Communications. 8: 229.
    Link to publisher’s version
    https://doi.org/10.1038/s41467-017-00194-3
    Type
    Article
    Collections
    Life Sciences Publications

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