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

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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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.

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Correspondence to Rosemary Loria or Gregory L Challis.

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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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