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  • Rewiring central carbon met...
    Guo, Wei; Huang, Qiulan; Feng, Yuhui; Tan, Taicong; Niu, Suhao; Hou, Shaoli; Chen, Zhigang; Du, Zhi‐Qiang; Shen, Yu; Fang, Xu

    Biotechnology and bioengineering, August 2020, Letnik: 117, Številka: 8
    Journal Article

    Metabolic engineering of Saccharomyces cerevisiae for high‐level production of aromatic chemicals has received increasing attention in recent years. Tyrosol production from glucose by S. cerevisiae is considered an environmentally sustainable and safe approach. However, the production of tyrosol and salidroside by engineered S. cerevisiae has been reported to be lower than 2 g/L to date. In this study, S. cerevisiae was engineered with a push‐pull‐restrain strategy to efficiently produce tyrosol and salidroside from glucose. The biosynthetic pathways of ethanol, phenylalanine, and tryptophan were restrained by disrupting PDC1, PHA2, and TRP3. Subsequently, tyrosol biosynthesis was enhanced with a metabolic pull strategy of introducing PcAAS and EcTyrAM53I/A354V. Moreover, a metabolic push strategy was implemented with the heterologous expression of phosphoketolase (Xfpk), and then erythrose 4‐phosphate was synthesized simultaneously by two pathways, the Xfpk‐based pathway and the pentose phosphate pathway, in S. cerevisiae. Furthermore, the heterologous expression of Xfpk alone in S. cerevisiae efficiently improved tyrosol production compared with the coexpression of Xfpk and phosphotransacetylase. Finally, the tyrosol yield increased by approximately 135‐folds, compared with that of parent strain. The total amount of tyrosol and salidroside with glucose fed‐batch fermentation was over 10 g/L and reached levels suitable for large‐scale production. Highest production of tyrosol and salidroside, obtained via introducing the Xfpk‐based pathway into S. cerevisiae, can pave a green, efficient and sustainable way for large‐scale production of tyrosol and salidroside.