Discovery of spectabilide A, a new cytotoxic cyclic lipodepsipeptide from Trichothecium spectabile comb. nov. (Ascomycota, Sordariomycetes) revealed by OSMAC-guided metabolomics

The biosynthetic potential of the fungal epiphyte Stanjemonium spectabile, isolated from the endemic plant Bupleurum gibraltaricum (Granada, Spain), was investigated combining OSMAC (One Strain, Many Compounds) and metabolomic approaches. A total of 78 cultivation conditions were evaluated using different media formulations based on substrate utilization profiles obtained from filamentous fungi nutritional array plates.

Chemical dereplication and MS / MS-based molecular networking revealed the production of a broad array of mycotoxins and bioactive compounds, including a novel cyclic lipodepsipeptide, namely spectabilide A. Phylogenetic studies, combined with a chemotaxonomic analysis of the annotated compounds, also supports that S. spectabile resides in the Trichothecium s. str. clade. The isolated compound spectabilide A, composed of three amino acids and a hydroxylated aliphatic side chain, displayed potent cytotoxic activity against breast adenocarcinoma cancer cell lines.

These findings highlight the potential of underexplored fungal taxa and cultivation strategies for the discovery of novel bioactive scaffolds and provide new insights into the chemical ecology and taxonomy of S. spectabile, resulting in the new combination Trichothecium spectabile comb. nov.