Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tong, Bingqi, Belcher, Bridget P., Nomura, Daniel K., Maimone, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
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
_version_ 1783716236377456640
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
work_keys_str_mv AT tongbingqi chemicalinvestigationsintothebiosynthesisofthegymnastatinanddankastatinalkaloids
AT belcherbridgetp chemicalinvestigationsintothebiosynthesisofthegymnastatinanddankastatinalkaloids
AT nomuradanielk chemicalinvestigationsintothebiosynthesisofthegymnastatinanddankastatinalkaloids
AT maimonethomasj chemicalinvestigationsintothebiosynthesisofthegymnastatinanddankastatinalkaloids