TY - JOUR
T1 - Euglenatides, potent antiproliferative cyclic peptides isolated from the freshwater photosynthetic microalga Euglena gracilis
AU - Ganesan, A.
AU - Aldholmi, Mohammed
AU - Ahmad, Rizwan
AU - Carretero-Molina, Daniel
AU - Pérez-Victoria, Ignacio
AU - Martín, Jesús
AU - Reyes, Fernando
AU - Genilloud, Olga
AU - Gourbeyre, Léa
AU - Gefflaut, Thierry
AU - Carlsson, Hanne
AU - Maklakov, Alexei
AU - Field, Robert A.
AU - O'Neill, Ellis
AU - Wilkinson, Barrie
AU - O'Connell, Maria
PY - 2022/3/24
Y1 - 2022/3/24
N2 - 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.
AB - 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.
KW - Antiproliferative
KW - Cyclic Peptides
KW - Microalgae
KW - Natural Products
KW - Nematodes
UR - http://www.scopus.com/inward/record.url?scp=85127596683&partnerID=8YFLogxK
U2 - 10.1002/anie.202203175
DO - 10.1002/anie.202203175
M3 - Article
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
SN - 1433-7851
ER -