Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside

Summary Tyrosol and its glycosylated product salidroside are important ingredients in pharmaceuticals, nutraceuticals and cosmetics. Despite the ability of Saccharomyces cerevisiae to naturally synthesize tyrosol, high yield from de novo synthesis remains a challenge. Here, we used metabolic enginee...

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Autores principales:	Huayi Liu, Yujuan Tian, Yi Zhou, Yeyi Kan, Tingting Wu, Wenhai Xiao, Yunzi Luo
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/4b6baa0feea3463a9e09073bb09a7277
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spelling	oai:doaj.org-article:4b6baa0feea3463a9e09073bb09a72772021-11-18T15:39:53ZMulti‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside1751-791510.1111/1751-7915.13667https://doaj.org/article/4b6baa0feea3463a9e09073bb09a72772021-11-01T00:00:00Zhttps://doi.org/10.1111/1751-7915.13667https://doaj.org/toc/1751-7915Summary Tyrosol and its glycosylated product salidroside are important ingredients in pharmaceuticals, nutraceuticals and cosmetics. Despite the ability of Saccharomyces cerevisiae to naturally synthesize tyrosol, high yield from de novo synthesis remains a challenge. Here, we used metabolic engineering strategies to construct S. cerevisiae strains for high‐level production of tyrosol and salidroside from glucose. First, tyrosol production was unlocked from feedback inhibition. Then, transketolase and ribose‐5‐phosphate ketol‐isomerase were overexpressed to balance the supply of precursors. Next, chorismate synthase and chorismate mutase were overexpressed to maximize the aromatic amino acid flux towards tyrosol synthesis. Finally, the competing pathway was knocked out to further direct the carbon flux into tyrosol synthesis. Through a combination of these interventions, tyrosol titres reached 702.30 ± 0.41 mg l−1 in shake flasks, which were approximately 26‐fold greater than that of the WT strain. RrU8GT33 from Rhodiola rosea was also applied to cells and maximized salidroside production from tyrosol in S. cerevisiae. Salidroside titres of 1575.45 ± 19.35 mg l−1 were accomplished in shake flasks. Furthermore, titres of 9.90 ± 0.06 g l−1 of tyrosol and 26.55 ± 0.43 g l−1 of salidroside were achieved in 5 l bioreactors, both are the highest titres reported to date. The synergistic engineering strategies presented in this study could be further applied to increase the production of high value‐added aromatic compounds derived from the aromatic amino acid biosynthesis pathway in S. cerevisiae.Huayi LiuYujuan TianYi ZhouYeyi KanTingting WuWenhai XiaoYunzi LuoWileyarticleBiotechnologyTP248.13-248.65ENMicrobial Biotechnology, Vol 14, Iss 6, Pp 2605-2616 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biotechnology TP248.13-248.65
spellingShingle	Biotechnology TP248.13-248.65 Huayi Liu Yujuan Tian Yi Zhou Yeyi Kan Tingting Wu Wenhai Xiao Yunzi Luo Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
description	Summary Tyrosol and its glycosylated product salidroside are important ingredients in pharmaceuticals, nutraceuticals and cosmetics. Despite the ability of Saccharomyces cerevisiae to naturally synthesize tyrosol, high yield from de novo synthesis remains a challenge. Here, we used metabolic engineering strategies to construct S. cerevisiae strains for high‐level production of tyrosol and salidroside from glucose. First, tyrosol production was unlocked from feedback inhibition. Then, transketolase and ribose‐5‐phosphate ketol‐isomerase were overexpressed to balance the supply of precursors. Next, chorismate synthase and chorismate mutase were overexpressed to maximize the aromatic amino acid flux towards tyrosol synthesis. Finally, the competing pathway was knocked out to further direct the carbon flux into tyrosol synthesis. Through a combination of these interventions, tyrosol titres reached 702.30 ± 0.41 mg l−1 in shake flasks, which were approximately 26‐fold greater than that of the WT strain. RrU8GT33 from Rhodiola rosea was also applied to cells and maximized salidroside production from tyrosol in S. cerevisiae. Salidroside titres of 1575.45 ± 19.35 mg l−1 were accomplished in shake flasks. Furthermore, titres of 9.90 ± 0.06 g l−1 of tyrosol and 26.55 ± 0.43 g l−1 of salidroside were achieved in 5 l bioreactors, both are the highest titres reported to date. The synergistic engineering strategies presented in this study could be further applied to increase the production of high value‐added aromatic compounds derived from the aromatic amino acid biosynthesis pathway in S. cerevisiae.
format	article
author	Huayi Liu Yujuan Tian Yi Zhou Yeyi Kan Tingting Wu Wenhai Xiao Yunzi Luo
author_facet	Huayi Liu Yujuan Tian Yi Zhou Yeyi Kan Tingting Wu Wenhai Xiao Yunzi Luo
author_sort	Huayi Liu
title	Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
title_short	Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
title_full	Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
title_fullStr	Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
title_full_unstemmed	Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
title_sort	multi‐modular engineering of saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/4b6baa0feea3463a9e09073bb09a7277
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Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside

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