Submitted to: Applied Microbiology and Biotechnology
Publication Type: Review Article
Publication Acceptance Date: 4/5/2020
Publication Date: 4/23/2020
Citation: Proctor, R.H., McCormick, S.P., Gutierrz, S. 2020. Genetic bases for variation in structure and biological activity of trichothecene toxins produced by diverse fungi. Applied Microbiology and Biotechnology. 104:5185–5199. https://doi.org/10.1007/s00253-020-10612-0.
Interpretive Summary: Trichothecenes are fungal toxins that pose a health risk to humans, livestock and pets because of their toxicity, and because they can contaminate crop plants used to make food and feed. The toxins are produced by diverse fungal species, including some fungi that cause disease on crops and other fungi that are used for biological control of fungal diseases or insect pests on crops. Over 200 different trichothecenes have been reported; they all have the same core chemical structure, but differ from one another by the presence and absence of various small chemical structures attached to different positions of the core structure. The differences in chemical structures can markedly affect toxicity of trichothecenes. This article reviews advances in understanding of the genetic and enzymatic bases for the differences in trichothecene structures that lead to differences in toxicity. Understanding the fungal genes and enzymes that are responsible for the structural differences has potential to contribute to strategies that detoxify trichothecenes and thereby protect humans and animals from the health hazards posed by the toxins.
Technical Abstract: Trichothecenes are sesquiterpene toxins produced by diverse but relatively few fungal species in at least three classes of Ascomycetes: Dothideomycetes, Eurotiomycetes and Sordariomycetes. Approximately 200 structurally distinct trichothecene analogs have been described, but a given fungal species typically produces only a small subset of the analogs. All trichothecenes share a core structure consisting of a four-ring nucleus known as 12,13-epoxytrichothec-9-ene. This structure can be substituted at various positions with hydroxyl, acyl or keto groups to give rise to the diversity of trichothecene structures that has been described. Over the last 30 years, the genetic and biochemical pathways required for trichothecene biosynthesis in several species of the fungi Fusarium and Trichoderma have been elucidated. In addition, phylogenetic and functional analyses of trichothecene biosynthetic (TRI) genes from fungi in multiple genera have provided insights into how acquisition, loss and changes in functions of TRI genes have given rise to the diversity of trichothecene structures. These analyses also suggest both divergence and convergence of TRI gene function during the evolutionary history of trichothecene biosynthesis. What has driven trichothecene structural diversification remains as unanswered question. However, insight into the role of trichothecenes in plant pathogenesis of Fusarium species and plant glucosyltransferases that can detoxify the toxins by glycosylating them point to a possible driver. Because the glucosyltransferases exhibit substrate specificity, changes in trichothecene structures produced by a fungus could allow it to evade trichothecene detoxification by the plant enzymes. Thus, it is possible that advantages conferred by evading detoxification drive trichothecene structural diversification.