Cargando…

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

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 inh...

Descripción completa

Detalles Bibliográficos
Autores principales: Aldholmi, Mohammed, Ahmad, Rizwan, Carretero‐Molina, Daniel, Pérez‐Victoria, Ignacio, Martín, Jesús, Reyes, Fernando, Genilloud, Olga, Gourbeyre, Léa, Gefflaut, Thierry, Carlsson, Hanne, Maklakov, Alexei, O'Neill, Ellis, Field, Robert A., Wilkinson, Barrie, O'Connell, Maria, Ganesan, A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321709/
https://www.ncbi.nlm.nih.gov/pubmed/35325497
http://dx.doi.org/10.1002/anie.202203175
_version_ 1784756114370330624
author Aldholmi, Mohammed
Ahmad, Rizwan
Carretero‐Molina, Daniel
Pérez‐Victoria, Ignacio
Martín, Jesús
Reyes, Fernando
Genilloud, Olga
Gourbeyre, Léa
Gefflaut, Thierry
Carlsson, Hanne
Maklakov, Alexei
O'Neill, Ellis
Field, Robert A.
Wilkinson, Barrie
O'Connell, Maria
Ganesan, A.
author_facet Aldholmi, Mohammed
Ahmad, Rizwan
Carretero‐Molina, Daniel
Pérez‐Victoria, Ignacio
Martín, Jesús
Reyes, Fernando
Genilloud, Olga
Gourbeyre, Léa
Gefflaut, Thierry
Carlsson, Hanne
Maklakov, Alexei
O'Neill, Ellis
Field, Robert A.
Wilkinson, Barrie
O'Connell, Maria
Ganesan, A.
author_sort Aldholmi, Mohammed
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9321709
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-93217092022-07-30 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 O'Neill, Ellis Field, Robert A. Wilkinson, Barrie O'Connell, Maria Ganesan, A. Angew Chem Int Ed Engl Research Articles 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. John Wiley and Sons Inc. 2022-04-06 2022-06-07 /pmc/articles/PMC9321709/ /pubmed/35325497 http://dx.doi.org/10.1002/anie.202203175 Text en © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Aldholmi, Mohammed
Ahmad, Rizwan
Carretero‐Molina, Daniel
Pérez‐Victoria, Ignacio
Martín, Jesús
Reyes, Fernando
Genilloud, Olga
Gourbeyre, Léa
Gefflaut, Thierry
Carlsson, Hanne
Maklakov, Alexei
O'Neill, Ellis
Field, Robert A.
Wilkinson, Barrie
O'Connell, Maria
Ganesan, A.
Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis
title Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis
title_full Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis
title_fullStr Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis
title_full_unstemmed Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis
title_short Euglenatides, Potent Antiproliferative Cyclic Peptides Isolated from the Freshwater Photosynthetic Microalga Euglena gracilis
title_sort euglenatides, potent antiproliferative cyclic peptides isolated from the freshwater photosynthetic microalga euglena gracilis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321709/
https://www.ncbi.nlm.nih.gov/pubmed/35325497
http://dx.doi.org/10.1002/anie.202203175
work_keys_str_mv AT aldholmimohammed euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT ahmadrizwan euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT carreteromolinadaniel euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT perezvictoriaignacio euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT martinjesus euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT reyesfernando euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT genilloudolga euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT gourbeyrelea euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT gefflautthierry euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT carlssonhanne euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT maklakovalexei euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT oneillellis euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT fieldroberta euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT wilkinsonbarrie euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT oconnellmaria euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis
AT ganesana euglenatidespotentantiproliferativecyclicpeptidesisolatedfromthefreshwaterphotosyntheticmicroalgaeuglenagracilis