Fungicides are often limited by poor efficacy and high toxicity. Our previous research identified perillyl alcohol (POH) as a promising plant-derived fungicide. Here, POH exhibits antifungal activity by inducing metacaspase-independent apoptosis in Botrytis cinerea. Furthermore, POH triggers both nonselective and selective autophagy, particularly endoplasmic reticulum autophagy (ER-phagy) and mitochondrial autophagy (mitophagy). Ubiquitylation analysis revealed that POH promotes protein ubiquitination. Additionally, transcriptome analysis revealed the suppression of Na/K-ATPase-related gene expression and activity. Importantly, we identified BcBet4 as a direct molecular target of POH, with binding interactions contributing to its mode of action. Through systematic chemical modifications, we developed POH-10, a derivative exhibiting enhanced antifungal efficacy and a stronger binding affinity to BcBet4. These findings provide valuable insights for the development of novel antifungal agents. As a multitarget fungicide, POH holds significant potential for economically and ecologically sustainable crop disease management.
Shen et al. (Tue,) studied this question.