Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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


  1. Scheible, W.R. et al. Plant Cell 15, 1781–1794 (2003).

    CAS  Article  Google Scholar 

  2. Kers, J.A. et al. Mol. Microbiol. 55, 1025–1033 (2005).

    CAS  Article  Google Scholar 

  3. Kers, J.A. et al. Nature 429, 79–82 (2004).

    CAS  Article  Google Scholar 

  4. Wach, M.J., Kers, J.A., Krasnoff, S.B., Loria, R. & Gibson, D.M. Nitric Oxide 12, 46–53 (2005).

    CAS  Article  Google Scholar 

  5. Johnson, E.G. et al. Mol. Microbiol. 73, 409–418 (2009).

    CAS  Article  Google Scholar 

  6. Winkler, R. & Hertweck, C. ChemBioChem 8, 973–977 (2007).

    CAS  Article  Google Scholar 

  7. Roncone, R., Barbieri, M., Monzani, E. & Casella, L. Coord. Chem. Rev. 250, 1286–1293 (2006).

    CAS  Article  Google Scholar 

  8. Buddha, M.R. et al. J. Biol. Chem. 279, 49567–49570 (2004).

    CAS  Article  Google Scholar 

  9. Sono, M., Roach, M.P., Coulter, E.D. & Dawson, J.H. Chem. Rev. 96, 2841–2888 (1996).

    CAS  Article  Google Scholar 

  10. Denisov, I.G., Makris, T.M., Sligar, S.G. & Schlichting, I. Chem. Rev. 105, 2253–2277 (2005).

    CAS  Article  Google Scholar 

  11. Quaroni, L.G. et al. Biochemistry 43, 16416–16431 (2004).

    CAS  Article  Google Scholar 

  12. Franke, A. et al. J. Am. Chem. Soc. 126, 4181–4191 (2004).

    CAS  Article  Google Scholar 

  13. Nakahara, K. et al. J. Biol. Chem. 268, 8350–8355 (1993).

    CAS  PubMed  Google Scholar 

  14. Bourn, W.R. & Babb, B. Nucleic Acids Res. 23, 3696–3703 (1995).

    CAS  Article  Google Scholar 

  15. Omura, T. & Sato, R. J. Biol. Chem. 239, 2379–2385 (1964).

    CAS  PubMed  Google Scholar 

  16. Schenkman, J.B., Remmer, H. & Estabrook, R.W. Mol. Pharmacol. 3, 113–123 (1967).

    CAS  PubMed  Google Scholar 

  17. Ishii, Y. et al. J. Pharm. Biomed. Anal. 44, 150–159 (2007).

    CAS  Article  Google Scholar 

  18. Ottoni, O., Cruz, R. & Krammer, N.H. Tetrahedr. Lett. 40, 1117–1120 (1999).

    CAS  Article  Google Scholar 

  19. Osborne, A.S., Som, P., Metcalf, J.L. & Phillips, R.S. Bioorg. Med. Chem. Lett. 18, 5750–5752 (2008).

    CAS  Article  Google Scholar 

Download references


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.

Author information

Authors and Affiliations



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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Methods and Supplementary Results (PDF 2012 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing