Alterations in Protein Phosphorylation and Arginine Biosynthesis Metabolism Confer β-Phenylethanol Tolerance in Saccharomyces cerevisiae

IF 3.5 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology and Bioengineering Pub Date : 2025-01-30 DOI:10.1002/bit.28936

Chenghan Yang, Yilin Ren, Li Zhang, Yina Li, Chunxia Wang, Haifeng Hang, Xiwei Tian, Ali Mohsin, Ju Chu, Yingping Zhuang

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Abstract

The aromatic compound β-phenylethanol (2-PE) is inherently toxic and can inhibit cell activity in Saccharomyces cerevisiae, making it highly challenging to enhance strain tolerance through rational design due to the lack of reliable connections between tolerance phenotype and genetic loci. This study employed adaptive laboratory evolution strategy to investigate the tolerance characteristics of S. cerevisiae S288C under inhibitory concentrations of 2-PE. The tolerant mutant SEC4.0 was characterized through comprehensive analysis of whole genome sequence, transcriptome, and phosphoproteome. The findings revealed that the high resistance of SEC4.0 was not primarily due to large-scale transcriptional upregulation of stress response genes, but rather through alterations in the phosphorylation levels of lipid-related pathways. PKC1 mutations that affect stress signal transduction and SPT3 mutations that affect arginine biosynthesis have been shown to significantly enhance 2-PE resistance. This study also investigated the effects of exogenous amino acid addition and synergistic effects with two key mutanted genes on 2-PE resistance. This study provides a foundation for enhancing yeast tolerance to this aromatic compound through rational design strategies.

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蛋白质磷酸化和精氨酸生物合成代谢的改变决定了酿酒酵母对β-苯乙醇的耐受性。

芳香化合物β-苯乙醇（2-PE）具有内在毒性，可以抑制酿酒酵母的细胞活性，由于耐受性表型与遗传位点之间缺乏可靠的联系，因此通过合理设计提高菌株耐受性非常具有挑战性。本研究采用适应性实验室进化策略，研究了酿酒酵母S288C在2-PE抑制浓度下的耐受性特征。通过全基因组序列、转录组和磷蛋白组的综合分析，对耐药突变体SEC4.0进行了鉴定。研究结果表明，SEC4.0的高抗性主要不是由于应激反应基因的大规模转录上调，而是通过脂质相关通路磷酸化水平的改变。影响胁迫信号转导的PKC1突变和影响精氨酸生物合成的SPT3突变已被证明可显著增强2-PE抗性。本研究还研究了外源氨基酸添加以及与两个关键突变基因的协同效应对2-PE抗性的影响。本研究为通过合理的设计策略提高酵母对该芳香化合物的耐受性提供了基础。

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来源期刊

Biotechnology and Bioengineering 工程技术-生物工程与应用微生物

CiteScore

7.90

自引率

5.30%

发文量

280

审稿时长

2.1 months

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