Euglenatides, potent antiproliferative cyclic peptides isolated from the freshwater photosynthetic microalga Euglena gracilis

Ganesan, A. ORCID:, Aldholmi, Mohammed, Ahmad, Rizwan, Carretero-Molina, Daniel, Pérez-Victoria, Ignacio, Martín, Jesús, Reyes, Fernando, Genilloud, Olga, Gourbeyre, Léa, Gefflaut, Thierry, Carlsson, Hanne, Maklakov, Alexei ORCID:, Field, Robert A., O'Neill, Ellis, Wilkinson, Barrie and O'Connell, Maria ORCID: (2022) Euglenatides, potent antiproliferative cyclic peptides isolated from the freshwater photosynthetic microalga Euglena gracilis. Angewandte Chemie-International Edition, 61 (23). ISSN 1433-7851

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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 IC 50 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.

Item Type: Article
Additional Information: Acknowledgements: This work was funded through a scholarship to MA from Imam Abdulrahman Bin Faisal University, Saudi Arabia. We are incredibly grateful to Dr Armin Bauer (Sanofi-Aventis, Germany) for the kind gift of Boc-L-anti-4,5-dihydroxynorvaline(4-TBDMS)-OEt. We thank Dr Mercedes de la Cruz and Dr Caridad Díaz (Fundación MEDINA, Spain) for their assistance with the antimicrobial assays.
Uncontrolled Keywords: antiproliferative,cyclic peptides,microalgae,natural products,nematodes,chemistry(all),catalysis,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Biological Sciences
Faculty of Science > School of Chemistry
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Depositing User: LivePure Connector
Date Deposited: 31 Mar 2022 09:31
Last Modified: 29 Mar 2024 23:32
DOI: 10.1002/anie.202203175


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