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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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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