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Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

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Sharma_2017_NC_GenoChemetics_CC.pdf (1.128Mb)
Date
09/08/2017
Author
Sharma, Sunil V.
Tong, Xiaoxue
Pubill-Ulldemolins, Cristina
Cartmell, Christopher
Bogosyan, Emma J. A.
Rackham, Emma J.
Marelli, Enrico
Hamed, Refaat B.
Goss, Rebecca J.M.
Funder
European Research Council
BBSRC
Grant ID
GCGXC
BB/M004570/1
Keywords
QD Chemistry
QH301 Biology
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)
NDAS
BDC
R2C
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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.
Citation
Sharma , S V , Tong , X , Pubill-Ulldemolins , C , Cartmell , C , Bogosyan , E J A , Rackham , E J , Marelli , E , Hamed , R B & Goss , R J M 2017 , ' Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo ' , Nature Communications , vol. 8 , 229 . https://doi.org/10.1038/s41467-017-00194-3
Publication
Nature Communications
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41467-017-00194-3
ISSN
2041-1723
Type
Journal article
Rights
© The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Description
We thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC consolidator grant GCGXC grant agreement no 614779) and ERAIB (Grant no. 031A338A) and H2020-MSCA-IF-2014 Grant no. 659399 for generous financial support.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/11518

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