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Functional diversification of epidithiodiketopiperazine methylation and oxidation towards pathogenic fungi

Summary

This research shows that Trichoderma hypoxylon, a beneficial fungus used in agriculture, produces different versions of antifungal compounds called epidithiodiketopiperazines (ETPs) to fight various harmful fungi. By deleting genes responsible for modifying these compounds, scientists found that different modifications work better against different pathogens—some modifications are more effective against mold fungi while others work better against grain pathogens. This demonstrates that the fungus uses chemical diversity as a strategy to protect crops from multiple threats.

Background

Trichoderma species are agriculturally beneficial fungi that produce diverse secondary metabolites, including epidithiodiketopiperazines (ETPs), which play vital roles in biocontrol mechanisms. Previous studies identified complex biosynthesis of α,β’-disulfide bridged ETPs with TdaH and TdaG catalyzing C6′-O-methylation and C4,C5-epoxidation respectively. The ecological functions of ETP structural diversity in natural environments remain poorly understood.

Objective

This study aimed to elucidate the functional diversification of ETP methylation and oxidation by TdaH and TdaG towards eleven pathogenic fungi, examining how structural modifications of ETPs contribute to Trichoderma hypoxylon’s biocontrol potential. The research sought to demonstrate the importance of ETP structural diversity in ecological adaptation and antagonistic effects against plant pathogens.

Results

Deletion of tdaH or tdaG reduced antagonistic abilities against most pathogenic fungi, with varying effects depending on the target pathogen. C6′-O-methylation showed higher antagonistic effects against B. cinerea (0.20), A. parasiticus (0.17), and V. alboatrum (0.16), while C4,C5-oxidation was more effective against F. nivale (0.40), F. graminearum (0.25), and C. cladosporioides (0.23). Co-evolution analysis confirmed that TdaH and TdaG proteins are highly conserved across fungi.

Conclusion

The structural diversity of ETPs driven by the catalytic promiscuity of Tda enzymes is essential for T. hypoxylon’s ecological adaptation and enhanced biocontrol capabilities against diverse pathogenic fungi. Different ETP modifications confer distinct antagonistic effects against specific pathogens, highlighting the importance of chemical diversity in fungal survival and pathogen suppression in agricultural settings.
  • Published in:Mycology,
  • Study Type:Experimental Study,
  • Source: PMID: 40937127; DOI: 10.1080/21501203.2025.2496190
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