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Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

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posted on 2023-06-09, 15:48 authored by Sunil V Sharma, Xiaoxue Tong, Cristina Pubill Ulldemolins, Christopher Cartmell, Emma J A Bogosyan, Emma J Rackham, Enrico Marelli, Refaat B Hamed, Rebecca J M Goss
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

History

Publication status

  • Published

File Version

  • Published version

Journal

Nature Communications

ISSN

2041-1723

Publisher

Nature Research

Issue

229

Volume

8

Page range

1-10

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-11-09

First Open Access (FOA) Date

2018-11-09

First Compliant Deposit (FCD) Date

2018-11-07

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