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

The mechanism for nitro group formation in the thaxtomin family of natural products is unknown. Genetic and biochemical studies now show the cytochrome P450 TxtE catalyzes this direct and regioselective nitration, using NO and O 2 to modify a tryptophan indole ring. Thaxtomin phytotoxins produced by...

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Bibliographic Details
Published in:	Nature chemical biology Vol. 8; no. 10; pp. 814 - 816
Main Authors:	Barry, Sarah M, Kers, Johan A, Johnson, Evan G, Song, Lijiang, Aston, Philip R, Patel, Bhumit, Krasnoff, Stuart B, Crane, Brian R, Gibson, Donna M, Loria, Rosemary, Challis, Gregory L
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-10-2012 Nature Publishing Group
Subjects:	631/1647/666/2259 631/92/60 631/92/603 Amino acids Biocatalysis Biochemical Engineering Biochemistry Bioorganic Chemistry Biosynthesis brief-communication Catalysis Cell Biology Chemistry Chemistry and Materials Science Chemistry/Food Science Cytochrome Cytochrome P-450 Enzyme System - metabolism Flowers & plants Indoles - metabolism Nitric oxide Nitric Oxide - metabolism Pathogens Phytotoxicity Phytotoxins Piperazines - metabolism Plants - microbiology Streptomyces - metabolism Toxins Tryptophan - metabolism
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Summary:	The mechanism for nitro group formation in the thaxtomin family of natural products is unknown. Genetic and biochemical studies now show the cytochrome P450 TxtE catalyzes this direct and regioselective nitration, using NO and O 2 to modify a tryptophan indole ring. 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 O 2 .
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711, USA Present address: Plant Pathology Department, University of Florida, PO Box 110680, Gainesville, FL 32611, USA Present address: Department of Chemistry, School of Biomedical Sciences, King’s College London, WC2R 2LS, UK Present address: Industrial Products Division, Intrexon Corporation, San Carlos, CA 94070, USA 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., analysed data. S.M.B., G.L.C., J.A.K., E.G.J, R.L. and B.R.C., wrote the paper. Present address: Citrus Research and Education Center, University of Florida, Lake Alfred, FL 33850, USA These authors contributed equally to this paper. Author Contributions
ISSN:	1552-4450 1552-4469
DOI:	10.1038/nchembio.1048