Song Na, Xia Huili, Yang Xiaoxue, Liu Siyao, Xu Linglong, Zhuang Kun, Yao Lan, Yang Shihui, Chen Xiong, Dai Jun
Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, No. 28, Nanli Road, Hongshan District, Wuhan, 430068, Hubei, People's Republic of China.
College of Biological and Food Engineering, Huanghuai University, Zhumadian, 463000, People's Republic of China.
Biotechnol Biofuels Bioprod. 2025 Mar 5;18(1):29. doi: 10.1186/s13068-025-02627-4.
Tyrosol is an important drug precursor, and Saccharomyces cerevisiae is one of the main microorganisms that produces tyrosol. Although excessive metabolic modification increases the production of tyrosol, it also causes a decrease in the growth rate of yeast. Therefore, this study attempted to restore the growth of S. cerevisiae through adaptive evolution and further improve tyrosol production.
After the adaptive laboratory evolution of S. cerevisiae S26, three evolutionary strains were obtained. The biomass of strain S26-AE2 reached 17.82 g DCW/L in the presence of 100 g/L glucose, which was 15.33% higher than that of S26, and its tyrosol production reached 817.83 mg/L. The transcriptome analysis revealed that, upon exposure to 100 g/L glucose, the S26-AE2 strain may reduce the transcriptional regulation of glucose repression through decreased HXK2 expression. The expression of genes related to pyruvate synthesis was increased in strain S26-AE2. Meanwhile, the expression levels of most tricarboxylic acid cycle-related genes in S26-AE2 were increased when cultured with 20 g/L glucose. Furthermore, the amount of tyrosol produced by strain S26 with the SNZ3 mutation increased by 17.01% compared with that of the control strain S26 following exposure to 100 g/L glucose.
In this study, a strain, S26-AE2, with good growth and tyrosol production performance was obtained by adaptive evolution. The transcriptome analysis revealed that the differences in the expression of genes involved in metabolic pathways in adaptive evolutionary strains may be related to yeast growth and tyrosol production. Further reverse engineering verified that the mutation of SNZ3 promoted tyrosol synthesis in S. cerevisiae in glucose-rich medium. This study provides a theoretical basis for the metabolic engineering of S. cerevisiae to synthesise tyrosol and its derivatives.
酪醇是一种重要的药物前体，酿酒酵母是生产酪醇的主要微生物之一。尽管过量的代谢修饰增加了酪醇的产量，但也导致酵母生长速率下降。因此，本研究试图通过适应性进化恢复酿酒酵母的生长并进一步提高酪醇产量。
对酿酒酵母S26进行适应性实验室进化后，获得了三株进化菌株。在含有100 g/L葡萄糖的条件下，菌株S26-AE2的生物量达到17.82 g DCW/L，比S26高15.33%，其酪醇产量达到817.83 mg/L。转录组分析表明，在暴露于100 g/L葡萄糖时，S26-AE2菌株可能通过降低HXK2表达来减少葡萄糖阻遏的转录调控。S26-AE2菌株中与丙酮酸合成相关的基因表达增加。同时，当在20 g/L葡萄糖条件下培养时，S26-AE2中大多数与三羧酸循环相关的基因表达水平增加。此外，在暴露于100 g/L葡萄糖后，具有SNZ3突变的S26菌株产生的酪醇量比对照菌株S26增加了17.01%。
本研究通过适应性进化获得了一株生长和酪醇生产性能良好的菌株S26-AE2。转录组分析表明，适应性进化菌株中参与代谢途径的基因表达差异可能与酵母生长和酪醇生产有关。进一步的反向工程验证了SNZ3突变促进了酿酒酵母在富含葡萄糖的培养基中合成酪醇。本研究为酿酒酵母代谢工程合成酪醇及其衍生物提供了理论依据。
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