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Thiostrepton tryptophan methyltransferase expands the chemistry of radical SAM enzymes


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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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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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.

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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).

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