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

PLoS Pathog. 2018 Apr 12;14(4):e1006946. doi: 10.1371/journal.ppat.1006946. eCollection 2018 Apr.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Fungal
  • Fungal Proteins / genetics*
  • Gene Expression Regulation, Fungal*
  • Genomics
  • Mycotoxins / chemistry*
  • Mycotoxins / pharmacology
  • Phylogeny*
  • Trichoderma / drug effects
  • Trichoderma / genetics*
  • Trichoderma / growth & development
  • Trichothecenes / chemistry*
  • Trichothecenes / pharmacology


  • DNA, Fungal
  • Fungal Proteins
  • Mycotoxins
  • Trichothecenes

Grants and funding

SG received funding from the Spanish Ministry of Economy and Competitiveness (grant number MINECO-AGL2015-70671-C2-2-R). TL received funding from the National Institute of Agricultural Sciences, Rural Development Administration (grant number PJ00843203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.