Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis

Summary The yeast Saccharomyces cerevisiae uses the pyruvate dehydrogenase‐bypass for acetyl‐CoA biosynthesis. This relatively inefficient pathway limits production potential for acetyl‐CoA‐derived biochemical due to carbon loss and the cost of two high‐energy phosphate bonds per molecule of acetyl‐...

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Autores principales:	Irfan Farabi Hayat, Manuel Plan, Birgitta E. Ebert, Geoff Dumsday, Claudia E. Vickers, Bingyin Peng
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/912b849ae4dd4eeab30401b22a5f7992
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spelling	oai:doaj.org-article:912b849ae4dd4eeab30401b22a5f79922021-11-18T15:39:53ZAuxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis1751-791510.1111/1751-7915.13880https://doaj.org/article/912b849ae4dd4eeab30401b22a5f79922021-11-01T00:00:00Zhttps://doi.org/10.1111/1751-7915.13880https://doaj.org/toc/1751-7915Summary The yeast Saccharomyces cerevisiae uses the pyruvate dehydrogenase‐bypass for acetyl‐CoA biosynthesis. This relatively inefficient pathway limits production potential for acetyl‐CoA‐derived biochemical due to carbon loss and the cost of two high‐energy phosphate bonds per molecule of acetyl‐CoA. Here, we attempted to improve acetyl‐CoA production efficiency by introducing heterologous acetylating aldehyde dehydrogenase and phosphoketolase pathways for acetyl‐CoA synthesis to enhance production of the sesquiterpene trans‐nerolidol. In addition, we introduced auxin‐mediated degradation of the glucose‐dependent repressor Mig1p to allow induced expression of GAL promoters on glucose so that production potential on glucose could be examined. The novel genes that we used to reconstruct the heterologous acetyl‐CoA pathways did not sufficiently complement the loss of endogenous acetyl‐CoA pathways, indicating that superior heterologous enzymes are necessary to establish fully functional synthetic acetyl‐CoA pathways and properly explore their potential for nerolidol synthesis. Notwithstanding this, nerolidol production was improved twofold to a titre of ˜ 900 mg l−1 in flask cultivation using a combination of heterologous acetyl‐CoA pathways and Mig1p degradation. Conditional Mig1p depletion is presented as a valuable strategy to improve the productivities in the strains engineered with GAL promoters‐controlled pathways when growing on glucose.Irfan Farabi HayatManuel PlanBirgitta E. EbertGeoff DumsdayClaudia E. VickersBingyin PengWileyarticleBiotechnologyTP248.13-248.65ENMicrobial Biotechnology, Vol 14, Iss 6, Pp 2627-2642 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biotechnology TP248.13-248.65
spellingShingle	Biotechnology TP248.13-248.65 Irfan Farabi Hayat Manuel Plan Birgitta E. Ebert Geoff Dumsday Claudia E. Vickers Bingyin Peng Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis
description	Summary The yeast Saccharomyces cerevisiae uses the pyruvate dehydrogenase‐bypass for acetyl‐CoA biosynthesis. This relatively inefficient pathway limits production potential for acetyl‐CoA‐derived biochemical due to carbon loss and the cost of two high‐energy phosphate bonds per molecule of acetyl‐CoA. Here, we attempted to improve acetyl‐CoA production efficiency by introducing heterologous acetylating aldehyde dehydrogenase and phosphoketolase pathways for acetyl‐CoA synthesis to enhance production of the sesquiterpene trans‐nerolidol. In addition, we introduced auxin‐mediated degradation of the glucose‐dependent repressor Mig1p to allow induced expression of GAL promoters on glucose so that production potential on glucose could be examined. The novel genes that we used to reconstruct the heterologous acetyl‐CoA pathways did not sufficiently complement the loss of endogenous acetyl‐CoA pathways, indicating that superior heterologous enzymes are necessary to establish fully functional synthetic acetyl‐CoA pathways and properly explore their potential for nerolidol synthesis. Notwithstanding this, nerolidol production was improved twofold to a titre of ˜ 900 mg l−1 in flask cultivation using a combination of heterologous acetyl‐CoA pathways and Mig1p degradation. Conditional Mig1p depletion is presented as a valuable strategy to improve the productivities in the strains engineered with GAL promoters‐controlled pathways when growing on glucose.
format	article
author	Irfan Farabi Hayat Manuel Plan Birgitta E. Ebert Geoff Dumsday Claudia E. Vickers Bingyin Peng
author_facet	Irfan Farabi Hayat Manuel Plan Birgitta E. Ebert Geoff Dumsday Claudia E. Vickers Bingyin Peng
author_sort	Irfan Farabi Hayat
title	Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis
title_short	Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis
title_full	Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis
title_fullStr	Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis
title_full_unstemmed	Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis
title_sort	auxin‐mediated induction of gal promoters by conditional degradation of mig1p improves sesquiterpene production in saccharomyces cerevisiae with engineered acetyl‐coa synthesis
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/912b849ae4dd4eeab30401b22a5f7992
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Auxin‐mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl‐CoA synthesis

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