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Cytochrome P450–catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis

Nature Chemical Biology volume 8, pages 814–816 (2012)Cite this article

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Abstract

Thaxtomin phytotoxins produced by plant-pathogenic Streptomyces species contain a nitro group that is essential for phytotoxicity. The N,N′-dimethyldiketopiperazine core of thaxtomins is assembled from L-phenylalanine and L-4-nitrotryptophan by a nonribosomal peptide synthetase, and nitric oxide synthase–generated NO is incorporated into the nitro group, but the biosynthesis of the nonproteinogenic amino acid L-4-nitrotryptophan is unclear. Here we report that TxtE, a unique cytochrome P450, catalyzes L-tryptophan nitration using NO and O2.

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Figure 1: Thaxtomin biosynthesis.
Figure 2: Characterization of purified recombinant TxtE.

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Acknowledgements

We thank P. Patel for assistance with fitting the L-tryptophan binding data to the one-site binding model. We also thank The UK Biotechnology and Biological Sciences Research Council (grant ref. BB/H006281/1 to G.L.C.) and the National Research Initiative of the United States Department of Agriculture Cooperative State Research, Education and Extension Service (grant no. 2008-35319-19202 to R.L.) for funding this research. The Bruker maXis mass spectrometer used in this research was obtained through Birmingham Science City: Innovative Uses for Advanced Materials in the Modern World with support from Advantage West Midlands and was partially funded by the European Regional Development Fund.

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Author notes

  1. Sarah M Barry, Johan A Kers, Evan G Johnson, Bhumit Patel & Rosemary Loria

    Present address: Present addresses: Department of Chemistry, School of Biomedical Sciences, King's College London, London, UK (S.M.B.); Industrial Products Division, Intrexon Corporation, San Carlos, California, USA (J.A.K.); Citrus Research and Education Center, University of Florida, Lake Alfred, Florida, USA (E.G.J.); Fraunhofer USA Center for Molecular Biotechnology, Newark, Delaware, USA (B.P.); Plant Pathology Department, University of Florida, Gainesville, Florida, USA (R.L.).,

  2. Sarah M Barry and Johan A Kers: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, University of Warwick, Coventry, UK

    Sarah M Barry, Lijiang Song, Philip R Aston & Gregory L Challis

  2. Department of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, New York, USA

    Johan A Kers, Evan G Johnson & Rosemary Loria

  3. Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA

    Bhumit Patel & Brian R Crane

  4. United States Department of Agriculture, Agricultural Research Service, Robert W. Holley Center for Agriculture and Health, Ithaca, New York, USA

    Stuart B Krasnoff & Donna M Gibson

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  1. Sarah M Barry
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Contributions

S.M.B., G.L.C., J.A.K., E.G.J. and R.L. designed the research. S.M.B., J.A.K., E.G.J., L.S., P.R.A. and B.P. performed the research. S.M.B., G.L.C., L.S., R.L., J.A.K., E.G.J., S.B.K., D.M.G. and B.R.C. analyzed data. S.M.B., G.L.C., J.A.K., E.G.J., R.L. and B.R.C. wrote the paper.

Corresponding authors

Correspondence to Rosemary Loria or Gregory L Challis.

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The authors declare no competing financial interests.

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Barry, S., Kers, J., Johnson, E. et al. Cytochrome P450–catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis. Nat Chem Biol 8, 814–816 (2012). https://doi.org/10.1038/nchembio.1048

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