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

Microbial Biotechnology - Tập 14 Số 6 - Trang 2605-2616 - 2021
Huayi Liu1, Yujuan Tian1, Yi Zhou1, Yeyi Kan1, Tingting Wu1, Wenhai Xiao2, Yunzi Luo1,2
1Department of Gastroenterology State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China
2Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China

Tóm tắt

SummaryTyrosol 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.

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Tài liệu tham khảo

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Microbial Biotechnology

Tập 14 Số 6

2605-2616

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