Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi

Authors: Proctor, Robert; McCormick, Susan; Kim, Hye-Seon; CARDOZA, ROSA - University Of Leon; Stanley, April; LINDO, LAURA - University Of Leon; Kelly, Amy; Brown, Daren; LEE, THERESA - Rural Development Administration - Korea; Vaughan, Martha; ALEXANDER, NANCY - Retired ARS Employee; Busman, Mark; GUTIERREZ, SANTIAGO - University Of Leon

Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2018
Publication Date: 4/12/2018
Citation: Proctor, R.H., McCormick, S.P., Kim, H.-S., Cardoza, R.E., Stanley, A.M., Lindo, L., Kelly, A., Brown, D.W., Lee, T., Vaughan, M.M., Alexander, N.J., Busman, M., Gutierrez, S. 2018. Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi. PLoS Pathogens. 14(4): e1006946. https://doi.org/10.1371/journal.ppat.1006946.
DOI: https://doi.org/10.1371/journal.ppat.1006946

Interpretive Summary: Trichothecenes are fungal toxins that frequently contaminate cereal grain and, as a result, pose health risks to humans and domestic animals. Grain contamination results when fungi infect cereal crops and produce trichothecenes in the infected tissue. Trichothecene production has been reported in at least 10 genera of fungi. Collectively, these fungi produce over 150 different trichothecenes, each with a similar but distinct chemical structure. Many of the structural differences increase or decrease the toxicity of trichothecenes and, thereby, their health risks. The objective of this study was to determine what genetic changes are responsible for the tremendous diversity of trichothecene structures produced by fungi. To meet this objective, we used chemical, genetic, and genome sequencing analyses to assess trichothecene production and genes responsible for biosynthesis of trichothecenes in nine fungal genera. The results indicate that acquisition, loss, and changes in function of the genes are responsible for the differences in chemical structures of trichothecenes. The results also indicate that some of the changes in structures have evolved independently in different fungi by acquisition of different genes with the same biochemical function. Together, the results explain the genetic causes of structural differences of trichothecenes that have been observed in crops and other materials. Differences in DNA sequences of the genes responsible for the structural differences can be used to develop DNA-based assays to determine the genetic potential of fungi to produce different trichothecenes and, therefore, the risks that the fungi pose to food and feed safety. Thus, the results benefit academic, government, and private-sector organizations that assess the risks that fungi pose to human and animal health.

Technical Abstract: Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus Fusarium are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some Fusarium species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (TRI) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in TRI gene duplication and number of TRI loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the TRI cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of TRI cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungi.