Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/19/2004
Publication Date: 5/6/2004
Citation: Kers, J., Wach, M., Krasnoff, S.B., Cameron, K.D., Bukhalid, R., Gibson, D.M., Crane, B.R., Loria, R. 2004. A bacterial nitric oxide synthase functions to nitrate a peptide phytotoxin. Nature. 429:79-82. Interpretive Summary: Several Streptomyces species cause "scab" diseases on potato tubers, sweet potato storage roots and expanded tap roots of radish, beet and similar crops. All of these species produce one or more members of an unusual nitrated dipeptide family known as thaxtomins. Toxin production occurs in diseased tissue and many of the disease symptoms are reproduced by the application of toxin preparations to susceptible plant tissue. In previous work, we have identified the enzymes involved in the formation of the dipeptide, but it was unclear as to how the nitrate group was added to the dipeptide. In this study, we provide evidence that the enzyme responsible is a nitric oxide synthase. The Streptomyces enzyme is very similar to the mammalian enzymes that produce nitric oxide, an important signal in cell communication, as well as to other bacterial nitric oxide synthases for which no biological function was known. This is the first instance of a biological role for nitric oxide synthase in production of a secondary metabolite.
Technical Abstract: Mammalian nitric oxide synthases (NOSs) oxidize L-arginine to nitric oxide (NO) for cell signaling and defense. Biological functions for bacterial NOSs are unknown. Here we describe a gene (nos) in the plant pathogen Streptomyces turgidiscabies that encodes a NOS homolog (stNOS) and reveal its role in nitrating the tryptophanyl moiety of the phytotoxin thaxtomin A. Thaxtomin production is essentially abolished by nos disruption and drastically reduced by NOS inhibitors. In vivo 15N incorporation shows the thaxtomin nitrate derives from L-arginine in a manner implicating NOS activity. High similarity among bacterial NOSs indicates a general function in nitrating secondary metabolites.