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

Abstract 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...

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Main Authors: Emily J. Johnston, Jess Tallis, Edward Cunningham-Oakes, Tessa Moses, Simon J. Moore, Sarah Hosking, Susan J. Rosser
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-40308-0
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author Emily J. Johnston
Jess Tallis
Edward Cunningham-Oakes
Tessa Moses
Simon J. Moore
Sarah Hosking
Susan J. Rosser
author_facet Emily J. Johnston
Jess Tallis
Edward Cunningham-Oakes
Tessa Moses
Simon J. Moore
Sarah Hosking
Susan J. Rosser
author_sort Emily J. Johnston
collection DOAJ
description Abstract 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 doaj.art-45fe8550be604c0293f915b1a5d6929d2023-11-26T12:56:00ZengNature PortfolioScientific Reports2045-23222023-08-0113111110.1038/s41598-023-40308-0Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escinEmily J. Johnston0Jess Tallis1Edward Cunningham-Oakes2Tessa Moses3Simon J. Moore4Sarah Hosking5Susan J. Rosser6Centre for Engineering Biology, University of EdinburghCentre for Engineering Biology, University of EdinburghDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of LiverpoolEdinOmics, RRID:SCR_021838, University of EdinburghGenetic Science Division, Thermo Fisher ScientificUnilever R&D Port SunlightCentre for Engineering Biology, University of EdinburghAbstract 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.https://doi.org/10.1038/s41598-023-40308-0
spellingShingle Emily J. Johnston
Jess Tallis
Edward Cunningham-Oakes
Tessa Moses
Simon J. Moore
Sarah Hosking
Susan J. Rosser
Yeast lacking the sterol C-5 desaturase Erg3 are tolerant to the anti-inflammatory triterpenoid saponin escin
Scientific Reports
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
url https://doi.org/10.1038/s41598-023-40308-0
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