title: Endogenic oxidative stress response contributes to glutathione over-accumulation in mutant Saccharomyces cerevisiae Y518.
abstract: 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.
authors.affiliation: School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, Jiangsu, 215500, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiang
authors.initials: J
authors.lastname: Sun
authors.forename: Yingyue
authors.initials: Y
authors.lastname: Zhu
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Qi
mesh_terms: D003545:Cysteine / Q000378:metabolism; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005978:Glutathione / Q000378:metabolism*; D016296:Mutagenesis; D009604:Nitrosoguanidines / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013312:Stress, Physiological; D014466:Ultraviolet Rays
chemical_list: D009604:Nitrosoguanidines; D017382:Reactive Oxygen Species; D014450:Electron Transport Complex III; D005978:Glutathione; D003545:Cysteine