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

Summary

Researchers studied fungi collected from Arctic driftwood to find new cancer-fighting compounds. Using advanced chemical analysis tools, they identified six different fungal strains and found that one strain, Acremonium synnematoferum, produced five unique compounds called depsipeptides. These compounds killed cancer cells in laboratory tests, showing promise as potential cancer treatments. This research highlights how extreme Arctic environments can harbor fungi with powerful medicinal properties.

Background

The Arctic environment hosts fungal communities adapted to extreme conditions that produce specialized bioactive secondary metabolites. Acremonium species remain underexplored despite their potential to produce structurally diverse and biologically active compounds. This study aimed to use an integrated workflow combining metabolomics, chemometrics, and bioactivity screening to prioritize Acremonium strains for identifying bioactive secondary metabolites.

Objective

To investigate six Acremonium strains associated with Arctic driftwood using metabolomics and chemometrics to identify cytotoxic secondary metabolites. The study focused on distinguishing phylogenetically related Acremonium species and prioritizing strains for isolation of bioactive compounds.

Results

Metabolomics analysis revealed unique chemical fingerprints for A. ellipsoideum (F1) and A. synnematoferum (F5). Strain F5 was prioritized based on metabolomic and bioactivity data. Five cyclic depsipeptides were isolated and identified: destruxin-A4 chlorohydrin, trichomide D, destruxin-A5, homodestruxin, and homodestcardin. All compounds exhibited cytotoxic effects against tested cancer cell lines, with compound 2 showing the most potent activity (IC50 of 40 nM against MCF7 and A2058 cells).

Conclusion

This is the first report of destruxin-family cyclic depsipeptides from Acremonium species, expanding the known chemical diversity of this genus. The multi-informative approach combining metabolomics, chemometrics, and bioactivity screening proved effective for fungal strain prioritization. Arctic fungi represent a valuable reservoir for bioactive compounds, and further research should focus on elucidating the cytotoxic mechanisms and optimizing selectivity of these destruxin-type compounds.
  • Published in:BMC Biotechnology,
  • Study Type:Research Study,
  • Source: PMC12642047, PMID: 41286812, doi: 10.1186/s12896-025-01065-2
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