文献类型：期刊文献

英文题名：Alterations in Protein Phosphorylation and Arginine Biosynthesis Metabolism Confer β-Phenylethanol Tolerance in Saccharomyces cerevisiae

作者：Yang, Chenghan[1];Ren, Yilin[1];Zhang, Li[1];Li, Yina[1];Wang, Chunxia[1];Hang, Haifeng[1,2];Tian, Xiwei[1,2];Mohsin, Ali[1];Chu, Ju[1,2];Zhuang, Yingping[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Qingdao Innovat Inst, Qingdao, Shandong, Peoples R China

年份：2025

卷号：122

期号：5

起止页码：1174

外文期刊名：BIOTECHNOLOGY AND BIOENGINEERING

收录：;EI(收录号：20250517792353);WOS:【SCI-EXPANDED(收录号:WOS:001409595300001)】；

基金：The research was funded by National Key Research and Development Program, China (2018YFA0900300), the Taishan Scholars Program of Shandong Province (NO. tsqn202312316), the Shanghai Pilot Program for Basic Research (22TQ1400100-14), the Natural Science Foundation of Shanghai(23ZR1416500), the Frontiers Science Center for Materiobiology and Dynamic Chemistry (JKVJ1231036). The authors appreciate technical assistance from Shanghai Applied Protein Technology Co. Ltd. (Shanghai, China) and Personalbio. Inc (Shanghai, China).

语种：英文

外文关键词：adaptive laboratory evolution; arginine; phosphoproteome; Saccharomyces cerevisiae; beta-phenylethanol

摘要：The aromatic compound beta-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.