Discovery of spectabilide A, a new cytotoxic cyclic lipodepsipeptide from Stanjemonium spectabile 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 Biolog FF microplates™. 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 with a molecular formula of C₂₈H₄₈N₄O₇, spectabilide A.

Spectabilide A, composed of three amino acids and a hydroxylated aliphatic side chain, displayed potent cytotoxic activity against five human cancer cell lines, particularly against breast adenocarcinoma MCF-7 (ED₅₀ = 0.11 µM). Phylogenetic and chemotaxonomic analyses further supported the reassignment of S. spectabile to the Trichothecium clade. 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 Stanjemonium spectabile .