Unlocking Marine Fungal Diversity: Discovery of Novel Peptaibols from Clonostachys rosea

Marine-derived fungi are increasingly recognized as a rich and still underexplored source of structurally unique and pharmacologically relevant secondary metabolites. Their adaptation to extreme marine environments promotes the production of chemically diverse compounds with remarkable biological activities, making them promising candidates for pharmaceutical and biotechnological applications. In this communication, the strain Clonostachys rosea IG119, isolated from the marine phanerogam Posidonia oceanica, was investigated as part of a project focused on bioactive metabolites from marine polyextremophilic fungi. Bio-guided assay analysis revealed that chloroform extract displayed antimicrobial activity against ESKAPEE pathogens. LC-MS/MS-based untargeted metabolomics combined with feature-based molecular networking (FBMN) allowed the annotation of several undescribed metabolites grouped into two main clusters corresponding to 11-mer and 10-mer peptaibols. Due to the structural complexity and low production yield of these compounds, an OSMAC (One Strain Many Compounds) approach was employed to optimize culture conditions and enhance metabolite production. This strategy led to the isolation and full chemical and biological characterization of two novel 11-mer and 10-mer peptaibols, Roseabols B and C, with distinctive structural features, while comprehensive molecular networking analysis enabled the exploration of the complete peptaibiome of the strain, further supported by genome analysis. These findings expand the known bioactive peptaibol landscape and highlight the biosynthetic versatility of C. rosea IG119.