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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

Microbial biotechnology, 2021-11, Vol.14 (6), p.2605-2616 [Periódico revisado por pares]

United States: John Wiley & Sons, Inc

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  • Título:
    Multi‐modular engineering of Saccharomyces cerevisiae for high‐titre production of tyrosol and salidroside
  • Autor: Liu, Huayi ; Tian, Yujuan ; Zhou, Yi ; Kan, Yeyi ; Wu, Tingting ; Xiao, Wenhai ; Luo, Yunzi
  • Assuntos: Amino acids ; Bioreactors ; Biosynthesis ; Cancer ; Carbon ; Chorismate mutase ; Coumaric acid ; Dehydrogenases ; Enzymes ; Genes ; Genetic engineering ; Glucose ; Glucosides ; Metabolic Engineering ; Metabolism ; Metabolites ; Modular engineering ; Mutation ; p-Coumaric acid ; Phenols ; Phenylethyl Alcohol - analogs & derivatives ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - genetics ; Salidroside ; Special Issue ; Tyrosol ; Yeast
  • É parte de: Microbial biotechnology, 2021-11, Vol.14 (6), p.2605-2616
  • Notas: Funding information
    We gratefully acknowledge the financial supports from the National Key R&D Program of China (Grant No. 2018YFA0903300), and the Natural Science Foundation of Tianjin City (Grant No. 19JCYBJC24200).
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  • Descrição: In this work, Liu et al. used metabolic engineering strategies to construct S. cerevisiae strains for high‐level production of tyrosol and salidroside from glucose. Finally, titers 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 titers reported to date. 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.
  • Editor: United States: John Wiley & Sons, Inc
  • Idioma: Inglês
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