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

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 sp. with the phytopathogen 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 sp. and   resulted in the isolation of five isochromanones from the whole co-culture extract, namely the known soudanones A, E, D (-) and their two new derivatives, soudanones H-I (-), the known isochromans, pseudoanguillosporins A and B (, ), naphtho--pyrones, cephalochromin and ustilaginoidin G (, ), and ergosterol (). Their structures were established by NMR, HR-ESIMS, FT-IR, electronic circular dichroism (ECD) spectroscopy, polarimetry ([α]), and Mosher's ester reaction. Bioactivity assays revealed antimicrobial activity of compounds and against the phytopathogens and , while pseudoanguillosporin A () showed the broadest and strongest anti-phytopathogenic activity against , , and . This is the first study assessing the anti-phytopathogenic activities of soudanones.