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
Publication statusPublished - 9 Aug 2017

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

View graph of relations

Related by author

  1. Natural products incorporating pyrimidine nucleosides

    Michailidou, F., Burnett, D. A., Sharma, S. V., Van Lanen, S. & Goss, R., 20 Feb 2020, Reference module in chemistry, molecular sciences and chemical engineering. Elsevier Inc.

    Research output: Chapter in Book/Report/Conference proceedingEntry for encyclopedia/dictionary

  2. A marine viral halogenase that iodinates diverse substrates

    Gkotsi, D. S., Ludewig, H., Sharma, S. V., Connolly, J. A., Dhaliwal, J., Wang, Y., Unsworth, W. P., Taylor, R. J. K., McLachlan, M. M. W., Shanahan, S., Naismith, J. H. & Goss, R. J. M., 14 Oct 2019, In : Nature Chemistry. 11, 12, p. 1091–1097 7 p.

    Research output: Contribution to journalArticle

  3. Buchwald Hartwig diversification of unprotected halotryptophans, halotryptophan containing tripeptides and the natural product barettin in aqueous conditions

    Renault, Y. J. G., Lynch, R., Marelli, E., Sharma, S. V., Pubill Ulldemolins, C., Sharp, J., Cartmell, C., Cárdenas, P. & Goss, R. J. M., 8 Oct 2019, In : Chemical Communications. Advance Article, 4 p.

    Research output: Contribution to journalReview article

  4. Heck diversification of indole‐based substrates under aqueous conditions: from indoles to unprotected halo‐tryptophans and halo‐tryptophans in natural product derivatives

    Pubill-Ulldemolins, C., Sharma, S. V., Cartmell, C., Zhao, J., Cárdenas, P. & Goss, R. J. M., 14 Aug 2019, In : Chemistry - A European Journal. 25, 46, p. 10866-10875 11 p.

    Research output: Contribution to journalArticle

  5. 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 6 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Nature Communications (Journal)

    Andy Gardner (Reviewer)
    Feb 2018

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

Related by journal

  1. 245 MHz bandwidth organic light-emitting diodes used in a gigabit optical wireless data link

    Yoshida, K., Manousiadis, P., Bian, R., Chen, Z., Murawski, C., Gather, M. C., Haas, H., Turnbull, G. A. & Samuel, I. D. W., 3 Mar 2020, In : Nature Communications. 11, 7 p., 1171.

    Research output: Contribution to journalArticle

  2. Anomalous fractionation of mercury isotopes in the Late Archean atmosphere

    Zerkle, A. L., Yin, R., Chen, C., Li, X., Izon, G. & Grasby, S., 6 Apr 2020, In : Nature Communications. 11, 9 p., 1709.

    Research output: Contribution to journalArticle

  3. Chronic bee paralysis as a serious emerging threat to honey bees

    Budge, G. E., Simcock, N. K., Holder, P. J., Shirley, M. D. F., Brown, M. A., Van Weymers, P. S. M., Evans, D. J. & Rushton, S. P., 1 May 2020, In : Nature Communications. 11, 9 p., 2164.

    Research output: Contribution to journalArticle

  4. High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations

    PCAWG Transcriptome Working Group, PCAWG Structural Variation Working Group, PCAWG Consortium, Zhang, Y., Chen, F., Fonseca, N. A., He, Y., Fujita, M., Nakagawa, H., Zhang, Z., Brazma, A., Amin, S. B., Awadalla, P., Bailey, P. J., Brazma, A., Brooks, A. N., Calabrese, C., Chateigner, A., Cortés-Ciriano, I., Craft, B. & 33 others, Craft, D., Creighton, C. J., Davidson, N. R., Demircioğlu, D., Erkek, S., Fonseca, N. A., Frenkel-Morgenstern, M., Goldman, M. J., Greger, L., Göke, J., He, Y., Hoadley, K. A., Hou, Y., Huska, M. R., Kahles, A., Khurana, E., Kilpinen, H., Korbel, J. O., Lamaze, F. C., Lehmann, K. V., Li, C., Li, S., Li, X., Li, X., Liu, D., Liu, F., Liu, X., Marin, M. G., Markowski, J., Meyerson, M., Nandi, T., Nielsen, M. M. & Lynch, A. G., 5 Feb 2020, In : Nature Communications. 11, 14 p., 736.

    Research output: Contribution to journalArticle

  5. Machine-learning-assisted insight into spin ice Dy2Ti2O7

    Samarakoon, A. M., Barros, K., Li, Y. W., Eisenbach, M., Zhang, Q., Ye, F., Sharma, V., Dun, Z. L., Zhou, H., Grigera, S. A., Batista, C. D. & Tennant, D. A., 14 Feb 2020, In : Nature Communications. 11, 9 p., 892.

    Research output: Contribution to journalArticle

ID: 250890459

Top