ARS | Publication request: Regiospecific cytochrome P450-catalyzed nitration of L-tryptophan in thaxtomin phytotoxin biosynthesis

Submitted to: Nature Chemical Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 7, 2012
Publication Date: September 2, 2012
Citation: Barry, S.M., Kers, J.A., Johnson, E.G., Song, L., Aston, P., Patel, B., Krasnoff, S., Crane, B.R., Gibson, D.M., Loria, R., Challis, G.L. 2012. Regiospecific cytochrome P450-catalyzed nitration of L-tryptophan in thaxtomin phytotoxin biosynthesis. Nature Chemical Biology. 8:814-816.

Interpretive Summary: Plant-pathogenic Streptomyces cause “scab” diseases on potato tubers, as well as other root crops, due to the presence of a small molecular weight phytotoxin, thaxtomin. Although the phytotoxin is known to be produced in part by the enzyme nitric oxide synthase, the mechanism by which the structure becomes nitrated has not been characterized. In this study, we were able to show that there is an additional enzyme required for the reaction and that the reaction is highly specific for the placement of the nitro- group onto the amino acid tryptophan. This study is the first report demonstrating the unique activity of the enzyme and its role in the production of thaxtomin, the principal metabolite involved in establishing the pathogen on the plant host.

Technical Abstract: Thaxtomins, phytotoxins produced by plant pathogenic Streptomyces species, contain a rare 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. Nitric oxide synthase-generated NO is incorporated into the nitro group of L-4-nitrotryptophan, but how this unique non-proteinogenic amino acid is biosynthesized is unclear. Here we show that TxtE, a novel cytochrome P450, catalyzes direct tryptophan nitration using NO and O2.