High glucose drives metabolic reprogramming toward stress resistance in Zygosaccharomyces mellis

Abstract This study aimed to elucidate transcriptional adaptation mechanisms in Zygosaccharomyces mellis under high-glucose (50%) conditions and to identify cellular processes involved in osmotic stress tolerance. Transcriptomic analysis was performed to characterize global gene expression changes in cells cultured in yeast extract-malt medium containing 50% glucose (G50). Genes involved in glycolysis, including GAL7 and FBP1, were downregulated, whereas PYC2, associated with the tricarboxylic acid cycle, was upregulated, suggesting suppression of fermentative metabolism and maintenance of respiratory activity. Genes involved in membrane phospholipid synthesis (AGPAT and PLPP) were downregulated, while an acid sphingomyelinase-like gene (ASM) was upregulated, suggesting altered membrane lipid metabolism under osmotic stress. In addition, the cytokinesis-related gene MYO1 was upregulated, suggesting structural reinforcement under osmotic stress. Furthermore, the growth of Δmmr1 and Δhxt4 mutants in Saccharomyces cerevisiae was significantly impaired under G50 conditions, highlighting the importance of mitochondrial inheritance and regulated glucose uptake. These findings suggest that Z. mellis adapts to high-glucose stress by coordinating changes in gene expression associated with respiratory activity, lipid metabolism, and cell division processes.