Skip to content

Research at St Andrews

Living GenoChemetics by hyphenating synthetic biology and synthetic chemistry in vivo

Research output: Contribution to journalArticle

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. 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. 2 Oct 2017 In : Angewandte Chemie International Edition. 56, 41, p. 12492-12497

    Research output: Contribution to journalArticle

  2. 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

  3. 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

  4. 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

  5. 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

Related by journal

  1. C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity

    Thangaraj Selvaraj , B. , Livesey , M. , Zhao , C. , Gregory , J. , James, O. , Cleary, E. , Chouhan, A. K. , Gane, A. , Perkins, E. , Dando, O. , Lillico, S. , Lee, Y-B. , Nishimura, A. , Poreci, U. , Thankamony, S. , Pray, M. , Vasistha, N. , Magnani, D. , Borooah, S. , Burr, K. & 12 others Story, D., McCampbell, A., Shaw, C., Kind, P., Aitman, T. J., Whitelaw, B., Wilmut, I., Smith, C., Miles, G. B., Hardingham, G., Wyllie, D. & Chandran, S. 24 Jan 2018 In : Nature Communications. 9, 14 p., 347

    Research output: Contribution to journalArticle

  2. A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

    Ladds, M. J. G. W. , van Leeuwen, I. M. M. , Drummond, C. J. , Chu, S. , Healy, A. R. , Popova, G. , Pastor-Fernández, A. , Mollick, T. , Darekar, S. , Sedimbi, S. K. , Nekulova, M. , Sachweh, M. C. C. , Campbell, J. , Higgins, M. , Tuck, C. , Popa, M. , Safont, M. M. , Gelebart, P. , Fandalyuk, Z. , Thompson, A. M. & 26 others Svensson, R., Gustavsson, A-L., Johansson, L., Färnegårdh, K., Yngve, U., Saleh, A., Haraldsson, M., D'Hollander, A. C. A., Franco, M., Zhao, Y., Håkansson, M., Walse, B., Larsson, K., Peat, E. M., Pelechano, V., Lunec, J., Vojtesek, B., Carmena, M., Earnshaw, W. C., McCarthy, A. R., Westwood, N. J., Arsenian-Henriksson, M., Lane, D. P., Bhatia, R., McCormack, E. & Laín, S. 16 Mar 2018 In : Nature Communications. 9, 1107

    Research output: Contribution to journalArticle

  3. A flow platform for degradation-free CuAAC bioconjugation

    Hatit, M. Z. C., Reichenbach, L. F., Tobin, J. M., Vilela, F., Burley, G. A. & Watson, A. J. B. 1 Oct 2018 In : Nature Communications. 9, 7 p., 4021

    Research output: Contribution to journalArticle

  4. Anion stabilised hypercloso-hexaalane Al6H6

    Bonyhady, S. J., Collis, D., Holzmann, N., Edwards, A. J., Piltz, R. O., Frenking, G., Stasch, A. & Jones, C. 6 Aug 2018 In : Nature Communications. 9, 6 p., 3079

    Research output: Contribution to journalArticle

  5. Coherently driven microcavity-polaritons and the question of superfluidity

    Juggins, R. T., Keeling, J. & Szymańska, M. H. 3 Oct 2018 In : Nature Communications. 9, 8 p., 4062

    Research output: Contribution to journalArticle

Related by journal

  1. Nature Communications (Journal)

    Gardner, A. (Reviewer)
    Feb 2018

    Activity: Publication peer-review and editorial workPeer review of manuscripts

ID: 250890459