Jul 2026· Letters in Applied Microbiology· Vol 79· 0 citations
Medicine
TL;DR
Z. mellis adapts to high-glucose stress by coordinating changes in gene expression associated with respiratory activity, lipid metabolism, and cell division processes, suggesting structural reinforcement under osmotic stress.
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.
Under severe stress, GO and KEGG enrichment consistently revealed the reinforcement of central carbon and energy metabolism, peroxisome-associated fatty acid turnover, oxidoreductase/redox activities, and translation and nucleotide metabolic pathways.
Dingkang Wang, Li Wang, Yue Xiao et al.· Journal of Proteome Research· 0 citations
Glycerol is a polyol that can be produced either chemically from oils or propylene, or biologically by yeasts, mainly under osmotic stress. Currently, glycerol is an abundant byproduct generated during biodiesel manufacturing that can be used as substrate in fermentative processes. Its efficient assimilation varies widely among yeast species; therefore, understanding the regulation of both transport and catabolism is pivotal for optimizing biotechnological processes based on this carbon source. This review addresses current knowledge on the regulatory networks controlling glycerol metabolism in yeasts, compassing transport mechanisms, metabolic pathways, transcriptional control and enzyme regulation. We highlight the distinct roles of the Stl1p symporter and Fps1p aquaglyceroporin in mediating glycerol flux across the plasma membrane, as well as the species-specific reliance on either the glycerol-3-phosphate (G3P) or dihydroxyacetone (DHA) pathway for glycerol assimilation. Classical biochemical studies have shown that glycerol catabolic enzymes are tightly regulated by carbon source availability, osmotic conditions, and feedback inhibition. Recently, transcriptomic and genetic analyses, particularly in Yarrowia lipolytica, show that the glycerol metabolism is governed by complex interactions between catabolite repression, nutrient signaling, and metabolic intermediates such as G3P, which acts as a key regulatory signal. Despite significant advances, regulatory mechanisms remain elusive in most non-conventional yeasts, underscoring the need for broader comparative studies. In addition, we review major metabolic engineering strategies aimed at enhancing glycerol utilization or redirecting carbon flux toward targeted bioproducts, emphasizing how mechanistic insights into glycerol metabolism and its regulation can guide the development of engineered strains with improved features for industrial applications. Lastly, we pointed out promising avenues for future research and biotechnological innovation.
Juliana Silva Carneiro Fonseca, W. B. da Silveira· World Journal of Microbiolog...· 0 citations
During high-concentration ethanol fermentation, Saccharomyces cerevisiae often faces multiple stresses, such as high osmotic pressure, ethanol toxicity, and nutrient limitation. These factors collectively limited the production of ethanol. To identify novel targets related to fermentation performance, we employed SHPERM- bCGHR strategy (a marker free allele replacement strategy based on comparative genomics and homologous recombination). We replaced the endogenous PHO4 of the high-producing strain MF01 with the PHO4 allele from MC15, thereby constructing a novel engineered strain MF01-PHO4. Under low-phosphate conditions, compared with the wildtype strain, the PHO5/11/12 genes and ribosomal protein genes showed significant upregulation in MF01-PHO4. These changes were associated with enhanced phosphorus uptake and protein synthesis. Under high phosphate conditions, the PHO4 expression and glycolytic enzyme gene expression in MF01-PHO4 were both lower than MF01, indicating that the substitution of the PHO4 allele may be associated with the coordinated changes in phosphate signal-mediated carbon phosphorus metabolism. This study identifies PHO4 as a promising candidate target for improving high concentration ethanol fermentation efficiency. These findings provide a framework to understand the phosphate-dependent regulatory effects of PHO4 allelic variation and offer a transferable strategy for strain improvement.
Simple Summary Renewable ethanol production from plant biomass is limited by inhibitory compounds generated during biomass processing. Syringaldehyde is a lignin-derived compound that reduces yeast fermentation efficiency, but the mechanisms underlying its toxicity and yeast adaptation remain unclear. In this study, we investigated how syringaldehyde affects Saccharomyces cerevisiae by combining fermentation analysis, cellular characterization, and gene expression analysis. We found that syringaldehyde strongly impaired ethanol production while only slightly affecting biomass accumulation, indicating that it primarily disrupted fermentative function rather than causing extensive growth inhibition. Further analyses showed that syringaldehyde induced multiple physiological stress responses, including alterations in cell envelope and increased membrane lipid oxidation. At the molecular level, yeast cells reduced the expression of genes related to protein production and cellular growth, while activating pathways involved in generating cellular reducing power and removing harmful aldehydes. These responses indicate that yeast cells adapt to syringaldehyde stress by reallocating metabolic resources from growth and ethanol production toward cellular protection and detoxification. This study improves understanding of microbial adaptation to lignin-derived aromatic aldehydes and provides insights for developing more robust yeast strains for sustainable bioethanol production.
Cells adapt to fluctuating nutrient conditions by dynamically regulating gene expression, ensuring survival under stress. Ygp1, a secretory yeast glycoprotein, is one such gene that is induced by nutrition deprivation, particularly glucose starvation. In this study, we investigated the regulatory mechanisms underlying nutrition-deprivation-responsive changes in gene expression, focusing on YGP1 expression. Under glucose-rich conditions, YGP1 expression was positively regulated by the RNA-binding protein Puf5, a member of the Puf family. This regulation ensured rhythmic YGP1 expression during M phase of the cell cycle. The Puf5-mediated control targeted a specific 60-nucleotide region in the YGP1 promoter (−600 to −540 from the start codon), and this regulation was partly mediated by the acid stress-responsive transcriptional activator Haa1. In addition, upon glucose exhaustion (diauxic shift), YGP1 expression was strongly induced by the stress-responsive transcription factors Msn2 and Msn4 through the stress-response elements in the YGP1 promoter. Further analysis of the physiological significance of YGP1 expression revealed that the Puf5-mediated regulation contributes to the acid stress responses, and YGP1 expression supports cell survival in the puf5Δ background. In summary, YGP1 expression is regulated by two distinct factors in a glucose availability-dependent manner: Puf5 under glucose-rich conditions and the Msn2/Msn4 during glucose starvation. Especially, Puf5-mediated regulation contributes to the acid stress responses and subsequently supports long-term cell survival.
Megumi Sato, Kaoru Irie, Yasuyuki Suda et al.· PLoS ONE· 0 citations
It is demonstrated that temperature can effectively reshape metabolic flux distribution and highlight transcription factor-mediated regulation as a practical target for improving precursor supply in engineered Y. lipolytica.
