Phenyl ether derivatives from a tobacco‐derived Aspergillus versicolor fungus and their activity against tobacco powdery mildew

BACKGROUND Since 1956, Aspergillus versicolor has been recognized to produce structurally diverse natural products. To address the need for novel antifungal agents, a phytochemical investigation was conducted on the tobacco‐derived A. versicolor YNCA0363, focusing on diphenyl ethers (DPEs) with unprecedented structures and antifungal activities. RESULTS Seven previously unreported DPEs (compounds 1 – 7 ) and two known DPEs (compounds 8 and 9 ) were isolated from A. versicolor YNCA0363. Compounds 1 – 3 possess a rare phenyl‐indole structure, compounds 4 and 5 feature a phenyl‐isoindoline hybrid, and compounds 6 and 7 exhibit a phenyl‐isochromene linkage that is distinct from previously reported DPEs. Compound 5 showed the strongest inhibition (86.1 ± 6.4%, median inhibitory concentration (IC 50 ) = 132.2 μg/mL) against Golovinomyces cichoracearum . Molecular docking revealed that DPEs interact with key tubulin residues (Ser243, Phe257, and Thr241). Microscopic analysis confirmed that compound 5 damaged the fungal conidia and hyphae. In addition, compound 5 induced tobacco defence enzymes and resistance‐related genes to enhance plant resistance. CONCLUSION This study expands the structural diversity of DPEs from A. versicolor , highlights their potential as effective antifungal agents, and underscores the importance of structural uniqueness in discovering emerging fungicides, providing valuable insights for agricultural antifungal development.