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Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids
Electrophilic natural products have provided fertile ground for understanding how nature inhibits protein function using covalent bond formation. The fungal strain Gymnascella dankaliensis has provided an especially interesting collection of halogenated cytotoxic agents derived from tyrosine which f...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246081/ https://www.ncbi.nlm.nih.gov/pubmed/34257889 http://dx.doi.org/10.1039/d1sc02613e |
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author | Tong, Bingqi Belcher, Bridget P. Nomura, Daniel K. Maimone, Thomas J. |
author_facet | Tong, Bingqi Belcher, Bridget P. Nomura, Daniel K. Maimone, Thomas J. |
author_sort | Tong, Bingqi |
collection | PubMed |
description | Electrophilic natural products have provided fertile ground for understanding how nature inhibits protein function using covalent bond formation. The fungal strain Gymnascella dankaliensis has provided an especially interesting collection of halogenated cytotoxic agents derived from tyrosine which feature an array of reactive functional groups. Herein we explore chemical and potentially biosynthetic relationships between architecturally complex gymnastatin and dankastatin members, finding conditions that favor formation of a given scaffold from a common intermediate. Additionally, we find that multiple natural products can also be formed from aranorosin, a non-halogenated natural product also produced by Gymnascella sp. fungi, using simple chloride salts thus offering an alternative hypothesis for the origins of these compounds in nature. Finally, growth inhibitory activity of multiple members against human triple negative breast cancer cells is reported. |
format | Online Article Text |
id | pubmed-8246081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-82460812021-07-12 Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids Tong, Bingqi Belcher, Bridget P. Nomura, Daniel K. Maimone, Thomas J. Chem Sci Chemistry Electrophilic natural products have provided fertile ground for understanding how nature inhibits protein function using covalent bond formation. The fungal strain Gymnascella dankaliensis has provided an especially interesting collection of halogenated cytotoxic agents derived from tyrosine which feature an array of reactive functional groups. Herein we explore chemical and potentially biosynthetic relationships between architecturally complex gymnastatin and dankastatin members, finding conditions that favor formation of a given scaffold from a common intermediate. Additionally, we find that multiple natural products can also be formed from aranorosin, a non-halogenated natural product also produced by Gymnascella sp. fungi, using simple chloride salts thus offering an alternative hypothesis for the origins of these compounds in nature. Finally, growth inhibitory activity of multiple members against human triple negative breast cancer cells is reported. The Royal Society of Chemistry 2021-05-31 /pmc/articles/PMC8246081/ /pubmed/34257889 http://dx.doi.org/10.1039/d1sc02613e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Tong, Bingqi Belcher, Bridget P. Nomura, Daniel K. Maimone, Thomas J. Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids |
title | Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids |
title_full | Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids |
title_fullStr | Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids |
title_full_unstemmed | Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids |
title_short | Chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids |
title_sort | chemical investigations into the biosynthesis of the gymnastatin and dankastatin alkaloids |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246081/ https://www.ncbi.nlm.nih.gov/pubmed/34257889 http://dx.doi.org/10.1039/d1sc02613e |
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