Induction of Isochromanones by Co-Cultivation of the Marine Fungus Cosmospora sp. and the Phytopathogen Magnaporthe   oryzae .

Microbial co-cultivation is a promising approach for the activation of biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. As part of our project aiming at the discovery of marine-derived fungal agrochemicals, we previously used four phytopathogens as model competitors in the co-cultivation of 21 marine fungal strains. Based on comparative untargeted metabolomics analyses and anti-phytopathogenic activities of the co-cultures, we selected the co-culture of marine Cosmospora sp. with the phytopathogen Magnaporthe oryzae for in-depth chemical studies. UPLC-MS/MS-based molecular networking (MN) of the co-culture extract revealed an enhanced diversity of compounds in several molecular families, including isochromanones, specifically induced in the co-culture. Large scale co-cultivation of Cosmospora sp. and M.   oryzae resulted in the isolation of five isochromanones from the whole co-culture extract, namely the known soudanones A, E, D ( 1 - 3 ) and their two new derivatives, soudanones H-I ( 4 - 5 ), the known isochromans, pseudoanguillosporins A and B ( 6 , 7 ), naphtho- γ -pyrones, cephalochromin and ustilaginoidin G ( 8 , 9 ), and ergosterol ( 10 ). Their structures were established by NMR, HR-ESIMS, FT-IR, electronic circular dichroism (ECD) spectroscopy, polarimetry ([α] D ), and Mosher's ester reaction. Bioactivity assays revealed antimicrobial activity of compounds 2 and 3 against the phytopathogens M. oryzae and Phytophthora infestans , while pseudoanguillosporin A ( 6 ) showed the broadest and strongest anti-phytopathogenic activity against Pseudomonas syringae , Xanthomonas campestris , M. oryzae and P. infestans . This is the first study assessing the anti-phytopathogenic activities of soudanones.