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Thiostrepton tryptophan methyltransferase expands the chemistry of radical SAM enzymes

Nature Chemical Biology volume 8, pages 957–959 (2012)Cite this article

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Abstract

Methylation is among the most widespread chemical modifications encountered in biomolecules and has a pivotal role in many major biological processes. In the biosynthetic pathway of the antibiotic thiostrepton A, we identified what is to our knowledge the first tryptophan methyltransferase. We show that it uses unprecedented chemistry to methylate inactivated sp2-hybridized carbon atoms, despite being predicted to be a radical SAM enzyme.

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Figure 1: Biosynthesis of thiostrepton A.
Figure 2: Analysis of the products formed by TsrM during reaction.
Figure 3: Activity and proposed mechanism for TsrM.

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Acknowledgements

We are grateful to J. Ulmer for critical reading of this manuscript. MS experiments were performed at Plateforme d'Analyse Protéomique de Paris Sud-Ouest. This work was supported by grants from the French National Research Agency to S.P.

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Author notes

  1. Alain Guillot and Alhosna Benjdia: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut National de la Recherche Agronomique (INRA), UMR 1319 Micalis, Jouy-en-Josas, France

    Stéphane Pierre, Alain Guillot, Philippe Langella & Olivier Berteau

  2. AgroParisTech, UMR Micalis, Jouy-en-Josas, France

    Stéphane Pierre, Alain Guillot, Philippe Langella & Olivier Berteau

  3. Department of Biomolecular Mechanisms, Max-Planck Institute for Medical Research, Heidelberg, Germany

    Alhosna Benjdia

  4. Department of Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden

    Corine Sandström

Authors
  1. Stéphane Pierre
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  2. Alain Guillot
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  3. Alhosna Benjdia
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  4. Corine Sandström
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  5. Philippe Langella
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  6. Olivier Berteau
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Contributions

The research was conceived by S.P., A.B. and O.B. S.P., A.B., A.G., C.S. and O.B. performed experiments. S.P., A.B., A.G., P.L. and O.B. analyzed the data. S.P., A.B. and O.B. wrote the manuscript.

Corresponding author

Correspondence to Olivier Berteau.

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The authors declare no competing financial interests.

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Pierre, S., Guillot, A., Benjdia, A. et al. Thiostrepton tryptophan methyltransferase expands the chemistry of radical SAM enzymes. Nat Chem Biol 8, 957–959 (2012). https://doi.org/10.1038/nchembio.1091

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