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Marine-derived Acremonium strain prioritization using untargeted metabolomics approach for the identification of cytotoxic cyclic depsipeptides

Summary

Researchers discovered five potent anti-cancer compounds from Arctic fungi called Acremonium strains. Using advanced chemical analysis techniques, they identified and tested these cyclic depsipeptides against various cancer cell types. The most active compound showed promising results against breast cancer and melanoma cells with extremely low concentrations needed for effect. These findings suggest Arctic microorganisms could be valuable sources for developing new cancer treatments.

Background

Arctic fungi have adapted to extreme environmental conditions by producing specialized bioactive secondary metabolites. Acremonium species remain underexplored despite their potential to produce structurally diverse and biologically active compounds. This study investigated six Arctic-derived Acremonium strains from driftwood to identify bioactive secondary metabolites using integrated metabolomics and chemometrics approaches.

Objective

To use an integrated workflow combining metabolomics, chemometrics, and bioactivity screening to prioritize Acremonium strains for identification of cytotoxic secondary metabolites. The study investigated six Acremonium strains (A. ellipsoideum F1-F2, A. synnematoferum F3-F5, and A. multiramosum F6) isolated from Arctic driftwood.

Results

Metabolomics and chemometrics revealed unique chemical fingerprints for A. ellipsoideum (F1) and A. synnematoferum (F5). Strain F5 was prioritized based on superior cytotoxic activity. Five cyclic depsipeptides were isolated: destruxin-A4 chlorohydrin (1), trichomide D (2), destruxin-A5 (3), homodestruxin (4), and homodestcardin (5). All compounds exhibited cytotoxic effects with compound 2 showing potent activity (IC50 40 nM) against MCF7 and A2058 cells.

Conclusion

The identification of five destruxin-type depsipeptides from A. synnematoferum represents the first report of these compounds from Acremonium species. Multi-informative-driven strain prioritization combining metabolomics, chemometrics, and bioactivity screening effectively uncovered bioactive metabolites. These findings highlight Arctic fungi as reservoirs of bioactive compounds and demonstrate the importance of exploring fungal diversity for drug development and understanding ecological roles.
  • Published in:BMC Biotechnology,
  • Study Type:Experimental Research,
  • Source: PMID: 41286812, DOI: 10.1186/s12896-025-01065-2
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