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Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
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 str...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601180/ https://www.ncbi.nlm.nih.gov/pubmed/32990403 http://dx.doi.org/10.1111/1751-7915.13667 |
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author | Liu, Huayi Tian, Yujuan Zhou, Yi Kan, Yeyi Wu, Tingting Xiao, Wenhai Luo, Yunzi |
author_facet | Liu, Huayi Tian, Yujuan Zhou, Yi Kan, Yeyi Wu, Tingting Xiao, Wenhai Luo, Yunzi |
author_sort | Liu, Huayi |
collection | PubMed |
description | 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 | Online Article Text |
id | pubmed-8601180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86011802021-11-24 Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside Liu, Huayi Tian, Yujuan Zhou, Yi Kan, Yeyi Wu, Tingting Xiao, Wenhai Luo, Yunzi Microb Biotechnol Special Issue Articles 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. John Wiley and Sons Inc. 2020-09-29 /pmc/articles/PMC8601180/ /pubmed/32990403 http://dx.doi.org/10.1111/1751-7915.13667 Text en © 2020 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Special Issue Articles Liu, Huayi Tian, Yujuan Zhou, Yi Kan, Yeyi Wu, Tingting Xiao, Wenhai Luo, Yunzi Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside |
title | 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_short | 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 |
topic | Special Issue Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601180/ https://www.ncbi.nlm.nih.gov/pubmed/32990403 http://dx.doi.org/10.1111/1751-7915.13667 |
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