Deletion of the Trichoderma virens NRPS, Tex7, induces accumulation of the anti-cancer compound heptelidic acid

Biochem Biophys Res Commun. 2020 Aug 27;529(3):672-677. doi: 10.1016/j.bbrc.2020.06.040. Epub 2020 Jul 18.


The anticancer antibiotic heptelidic acid is a sesquiterpene lactone produced by the beneficial plant fungus Trichoderma virens. This species has been separated into two strains, referred to as P and Q, based on its biosynthesis of secondary metabolites; notably, only P-strains were reported to produce heptelidic acid. While characterizing a Q-strain of T. virens containing a directed mutation in the non-ribosomal peptide synthetase encoding gene Tex7, the appearance of an unknown compound in anomalously large quantities was visualized by TLC. Using a combination of HPLC, LC-MS/MS, and NMR spectroscopy, this compound was identified as heptelidic acid. This discovery alters the strain classification structure of T. virens. Additionally, the Tex7 mutants inhibited growth of maize seedlings, while retaining the ability to induce systemic resistance against the foliar fungal pathogen, Cochliobolus heterostrophus.

Keywords: Heptelidic acid; Non-ribosomal peptide synthetase; Secondary metabolism; Trichoderma virens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / metabolism*
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Deletion
  • Genes, Fungal
  • Multigene Family
  • Peptide Synthases / genetics*
  • Peptide Synthases / metabolism
  • Sesquiterpenes / metabolism
  • Trichoderma / genetics*
  • Trichoderma / metabolism
  • Zea mays / growth & development
  • Zea mays / microbiology


  • Antibiotics, Antineoplastic
  • Fungal Proteins
  • Sesquiterpenes
  • heptelidic acid
  • Peptide Synthases
  • non-ribosomal peptide synthase