Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis

Aldholmi, Mohammed; Ahmad, Rizwan; Carretero-Molina, Daniel; Pérez-Victoria, Ignacio; Martín, Jesús; Reyes, Fernando; Genilloud, Olga; Gourbeyre, Léa; Gefflaut, Thierry; Carlsson, Hanne; Maklakov, Alexei; Field, Robert A.; O'Neill, Ellis; Wilkinson, Barrie; O'Connell, Maria; Ganesan, A.

Abstract

By limiting the nitrogen source to glutamic acid, we isolated cyclic peptides from Euglena gracilis containing asparagine and non-proteinogenic amino acids. Structure elucidation was accomplished through spectroscopic methods, mass spectrometry and chemical degradation. The euglenatides potently inhibit pathogenic fungi and cancer cell lines e.g., euglenatide B exhibiting IC50 values of 4.3 μM in Aspergillus fumigatus and 0.29 μM in MCF-7 breast cancer cells. In an unprecedented convergence of non-ribosomal peptide synthetase and polyketide synthase assembly-line biosynthesis between unicellular species and the metazoan kingdom, euglenatides bear resemblance to nemamides from Caenorhabditis elegans and inhibited both producing organisms E. gracilis and C. elegans. By molecular network analysis, we detected over forty euglenatide-like metabolites in E. gracilis, E. sanguinea and E. mutabilis, suggesting an important biological role for these natural products.

Citation

Aldholmi, M., Ahmad, R., Carretero-Molina, D., Pérez-Victoria, I., Martín, J., Reyes, F., Genilloud, O., Gourbeyre, L., Gefflaut, T., Carlsson, H., Maklakov, A., Field, R. A., O'Neill, E., Wilkinson, B., O'Connell, M., & Ganesan, A. (2022). Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis. Angewandte Chemie International Edition, 61(23), Article e202203175. https://doi.org/10.1002/anie.202203175

• Journal Article Type: Article
• Acceptance Date: Mar 23, 2022
• Online Publication Date: Mar 24, 2022
• Publication Date: Jun 7, 2022
• Deposit Date: Apr 25, 2022
• Publicly Available Date: Apr 25, 2022
• Journal: Angewandte Chemie - International Edition
• Print ISSN: 1433-7851
• Electronic ISSN: 1521-3773
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 61
• Issue: 23
• Article Number: e202203175
• DOI: https://doi.org/10.1002/anie.202203175
• Keywords: General Chemistry; Catalysis
• Public URL: https://nottingham-repository.worktribe.com/output/7678856
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/anie.202203175