Skip to content

Research at St Andrews

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

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

School/Research organisations

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.

Close

Details

Original languageEnglish
Article number229
Number of pages10
JournalNature Communications
Volume8
DOIs
StatePublished - 9 Aug 2017

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Sonogashira diversification of unprotected halotryptophans, halotryptophan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water

    Corr, M. J., Sharma, S. V., Pubill Ulldemolins, C., Bown, R. T., Poirot, P., Smith, D. R. M., Cartmell, C., Abou Fayad, A. & Goss, R. J. M. 1 Mar 2017 In : Chemical Science. 8, 3, p. 2039-2046 8 p.

    Research output: Contribution to journalArticle

  2. Rapid enzyme regeneration results in the striking catalytic longevity of an engineered, single species, biocatalytic biofilm

    Tong, X., Barberi, T. T., Botting, C. H., Sharma, S. V., Simmons, M. J. H., Overton, T. W. & Goss, R. J. M. 21 Oct 2016 In : Microbial Cell Factories. 15, 1, 11 p., 180

    Research output: Contribution to journalArticle

  3. A one-pot synthesis of symmetrical and unsymmetrical dipeptide ureas

    Abou Fayad, A., Pubill Ulldemolins, C., Sharma, S. V., Day, D. & Goss, R. J. M. Sep 2015 In : European Journal of Organic Chemistry. 25, p. 5603-5609 8 p.

    Research output: Contribution to journalArticle

  4. Pac13 is a small, monomeric dehydratase that mediates the formation of the 3′-deoxy nucleoside of pacidamycins

    Michailidou, F., Chung, C., Brown, M. J. B., Bent, A. F., Naismith, J. H., Leavens, W. J., Lynn, S. M., Sharma, S. V. & Goss, R. J. M. 30 Aug 2017 In : Angewandte Chemie International Edition. Early View

    Research output: Contribution to journalArticle

  5. Mild, aqueous α-arylation of ketones: towards new diversification tools for halogenated metabolites and drug molecules

    Marelli, E., Renault, Y., Sharma, S. V., Nolan, S. P. & Goss, R. J. M. 17 Mar 2017 In : Chemistry - A European Journal. 23, 16, p. 3832-3836 5 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Mating system manipulation and the evolution of sex-biased gene expression in Drosophila

    Veltsos, P., Fang, Y., Cossins, A. R., Snook, R. R. & Ritchie, M. G. 12 Dec 2017 In : Nature Communications. 8, 11 p., 2072

    Research output: Contribution to journalArticle

  2. Dissipatively coupled waveguide networks for coherent diffusive photonics

    Mukherjee, S., Mogilevtsev, D., Slepyan, G. Y., Doherty, T. H., Thomson, R. R. & Korolkova, N. 4 Dec 2017 In : Nature Communications. 8, 6 p., 1909

    Research output: Contribution to journalArticle

  3. Taking the pulse of Mars via dating of a plume-fed volcano

    Cohen, B. E., Mark, D. F., Cassata, W. S., Lee, M. R., Tomkinson, T. & Smith, C. L. Dec 2017 In : Nature Communications. 8, 9 p., 640

    Research output: Contribution to journalArticle

  4. Demonstration of chemistry at a point through restructuring and catalytic activation at anchored nanoparticles

    Neagu, D., Papaioannou, E. I., Ramli, W. K. W., Miller, D. N., Murdoch, B. J., Ménard, H., Umar, A., Barlow, A. J., Cumpson, P. J., Irvine, J. T. S. & Metcalfe, I. S. 30 Nov 2017 In : Nature Communications. 8, 1855

    Research output: Contribution to journalArticle

  5. Counter-intuitive influence of Himalayan river morphodynamics on Indus Civilisation urban settlements

    Singh, A., Thomsen, K. J., Sinha, R., Buylaert, J-P., Carter, A., Mark, D. F., Mason, P. J., Densmore, A. L., Murray, A. S., Jain, M., Paul, D. & Gupta, S. 28 Nov 2017 In : Nature Communications. 8, 14 p., 1617

    Research output: Contribution to journalArticle

ID: 250890459