Uncovering new antibiofilm roseabols from marine Clonostachys rosea through structural and multiomics approaches

Through a combined approach, that involved the one-strain-many-compounds (OSMAC) culturing approach, metabolomic andgenomic studies, and bioassay-guided purification we disclose the marine fungus Clonostachys rosea as producer of a family ofpeptaibols with new structural features. HRMS/MS, NMR, and advanced Marfey’s analysis enabled the structural elucidation of twomajor compounds of the roseabol family, named roseabols B (1) and C (2). Molecular networking further revealed a highly diverse andmicroheterogeneous peptaibol profile. Biological evaluation highlighted the ability of the isolated peptaibols to inhibit biofilmformation against Escherichia coli and Candida albicans . Overall, these studies demonstrate the effectiveness of metabolomics-drivenstrategies in discovering novel natural products and identify marine-derived peptaibols as promising antibiofilm agents.