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Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin

Escin is a mixture of over 30 glycosylated triterpenoid (saponin) structures, extracted from the dried fruit of horse chestnuts. Escin is currently used as an anti-inflammatory, and has potential applications in the treatment of arthritis and cancer. Engineered yeast would enable production of speci...

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Autores principales: Johnston, Emily J., Tallis, Jess, Cunningham-Oakes, Edward, Moses, Tessa, Moore, Simon J., Hosking, Sarah, Rosser, Susan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442444/
https://www.ncbi.nlm.nih.gov/pubmed/37604855
http://dx.doi.org/10.1038/s41598-023-40308-0
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author Johnston, Emily J.
Tallis, Jess
Cunningham-Oakes, Edward
Moses, Tessa
Moore, Simon J.
Hosking, Sarah
Rosser, Susan J.
author_facet Johnston, Emily J.
Tallis, Jess
Cunningham-Oakes, Edward
Moses, Tessa
Moore, Simon J.
Hosking, Sarah
Rosser, Susan J.
author_sort Johnston, Emily J.
collection PubMed
description Escin is a mixture of over 30 glycosylated triterpenoid (saponin) structures, extracted from the dried fruit of horse chestnuts. Escin is currently used as an anti-inflammatory, and has potential applications in the treatment of arthritis and cancer. Engineered yeast would enable production of specific bioactive components of escin at industrial scale, however many saponins have been shown to be toxic to yeast. Here we report that a Saccharomyces cerevisiae strain specifically lacking the sterol C-5 desaturase gene ERG3, exhibits striking enhanced tolerance to escin treatment. Transcriptome analyses, as well as pre-mixing of escin with sterols, support the hypothesis that escin interacts directly with ergosterol, but not as strongly with the altered sterols present in erg3Δ. A diverse range of saponins are of commercial interest, and this research highlights the value of screening lipidome mutants to identify appropriate hosts for engineering the industrial production of saponins.
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spelling pubmed-104424442023-08-23 Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin Johnston, Emily J. Tallis, Jess Cunningham-Oakes, Edward Moses, Tessa Moore, Simon J. Hosking, Sarah Rosser, Susan J. Sci Rep Article Escin is a mixture of over 30 glycosylated triterpenoid (saponin) structures, extracted from the dried fruit of horse chestnuts. Escin is currently used as an anti-inflammatory, and has potential applications in the treatment of arthritis and cancer. Engineered yeast would enable production of specific bioactive components of escin at industrial scale, however many saponins have been shown to be toxic to yeast. Here we report that a Saccharomyces cerevisiae strain specifically lacking the sterol C-5 desaturase gene ERG3, exhibits striking enhanced tolerance to escin treatment. Transcriptome analyses, as well as pre-mixing of escin with sterols, support the hypothesis that escin interacts directly with ergosterol, but not as strongly with the altered sterols present in erg3Δ. A diverse range of saponins are of commercial interest, and this research highlights the value of screening lipidome mutants to identify appropriate hosts for engineering the industrial production of saponins. Nature Publishing Group UK 2023-08-21 /pmc/articles/PMC10442444/ /pubmed/37604855 http://dx.doi.org/10.1038/s41598-023-40308-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Johnston, Emily J.
Tallis, Jess
Cunningham-Oakes, Edward
Moses, Tessa
Moore, Simon J.
Hosking, Sarah
Rosser, Susan J.
Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
title Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
title_full Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
title_fullStr Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
title_full_unstemmed Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
title_short Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
title_sort yeast lacking the sterol c-5 desaturase erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442444/
https://www.ncbi.nlm.nih.gov/pubmed/37604855
http://dx.doi.org/10.1038/s41598-023-40308-0
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