caa a22 4500 605502935 CHVBK 20210128100608.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00253-015-6629-7 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6629-7 Endogenic oxidative stress response contributes to glutathione over-accumulation in mutant Saccharomyces cerevisiae Y518 [Elektronische Daten] [Yibo Zhu, Jiang Sun, Yingyue Zhu, Limei Wang, Bin Qi] Mechanisms of glutathione (GSH) over-accumulation in mutant Saccharomyces cerevisiae Y518 screened by ultraviolet and nitrosoguanidine-induced random mutagenesis were studied. Y518 accumulated higher levels of GSH and l-cysteine than its wild-type strain. RNA-Seq and pathway enrichment analysis indicated a difference in the expression of key genes involved in cysteine production, the GSH biosynthesis pathway, and antioxidation processes. GSH1, MET17, CYS4, GPX2, CTT1, TRX2, and SOD1 and the transcriptional activators SKN7 and YAP1 were up-regulated in the mutant. Moreover, Y518 showed a dysfunctional respiratory chain resulting from dramatically weakened activity of complex III and significant elevation of intracellular reactive oxygen species (ROS) levels. The supplementation of antimycin A in the culture of the parent strain showed equivalent changes of ROS and GSH level. This study indicates that defective complex III prompts abundant endogenic ROS generation, which triggers an oxidative stress response and upregulation of gene expression associated with GSH biosynthesis. This finding may be helpful for developing new strategies for GSH fermentation process optimization or metabolic engineering. Springer-Verlag Berlin Heidelberg, 2015 Glutathione nationallicence Endogenic reactive oxygen stress nationallicence RNA-Seq nationallicence Malfunctional respiratory chain nationallicence Saccharomyces cerevisiae nationallicence Zhu Yibo School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut Sun Jiang School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut Zhu Yingyue School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut Wang Limei School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut Qi Bin School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/17(2015-09-01), 7069-7078 0175-7598 99:17<7069 2015 99 253 https://doi.org/10.1007/s00253-015-6629-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6629-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhu Yibo School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut NATIONALLICENCE 700 1- Sun Jiang School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut NATIONALLICENCE 700 1- Zhu Yingyue School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut NATIONALLICENCE 700 1- Wang Limei School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut NATIONALLICENCE 700 1- Qi Bin School of Biotechnology and Food Engineering, Changshu Institute of Technology, 215500, Changshu, Jiangsu, China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/17(2015-09-01), 7069-7078 0175-7598 99:17<7069 2015 99 253