Integrated Multiomics Elucidates Glutathione Metabolic Regulation in a Marine Aromatic Probiotic Yeast Meyerozyma guilliermondii GXDK6 under Salt Stress.

High-salt environments impose significant oxidative stress on microorganisms by disrupting redox homeostasis, necessitating efficient adaptive mechanisms such as glutathione (GSH) metabolism. Meyerozyma guilliermondii GXDK6, a marine-derived multistress-tolerant probiotic yeast, exhibits robust salt tolerance; however, the molecular basis of its GSH-mediated regulatory networks under salt stress remains unexplored. In this study, a comprehensive multiomics approach, integrating whole-genome sequencing, transcriptomics, and proteomics profiling, along with targeted physiological assays, was employed to investigate GSH metabolic regulation under salt stress. Genome-wide analysis identified 55 genes involved in other amino acid metabolism, with transcriptomic and proteomic profiling revealing salt-induced upregulation of key GSH biosynthetic genes (GSS, cysK_2, and glyA) and downregulation of degradation-related gene ggt_2. Moreover, transcript and protein level analyses demonstrated the activation of the biosynthetic pathway. Intracellular GSH content exhibited a biphasic response, with a 39.75% reduction at 5% NaCl, followed by a 53.01% increase at 10% NaCl. Glutathione S-transferase enzyme activity was significantly increased under salt stress, highlighting its role in cellular detoxification. Furthermore, exogenous application of GSH (10 mg/L) markedly improved halotolerance, resulting in a 52.7-fold increase in colony-forming units under 10% NaCl conditions. These findings highlight the crucial role of GSH in maintaining redox homeostasis and provide valuable insights for engineering microbial resilience in hypersaline environments.