Wine fermentation and flavor development are mediated by complex microbial interactions. Previous studies have shown that coinoculation with Oenococcus oeni can alter acid composition and aroma, yet the underlying transcriptional responses of S. cerevisiae and the metabolic strategies adopted by both species remain poorly understood. In this study, we performed mixed fermentation of S. cerevisiae and O. oeni, dividing the process into 6 representative stages for stage-specific analysis. Comparative evaluation with pure S. cerevisiae fermentation revealed that the presence of O. oeni reshaped both the acid profile and aromatic complexity of wine, while also influencing the growth kinetics of S. cerevisiae. Time-resolved transcriptomics demonstrated that O. oeni markedly altered the transcriptional dynamics of S. cerevisiae through changing the magnitude of transcriptional level while incurring opposite regulatory patterns in a small set of genes involved in stress responses and sulfur metabolism. Through the integration of a community genome-scale metabolic model with stage-resolved transcriptomic constraints, we resolved dynamic flux distributions of the mixed fermentation (MF) system and further revealed the metabolic impact of O. oeni on S. cerevisiae and MF. O. oeni exhibited low competitiveness for glucose but actively utilized fructose to generate energy through the phosphoketolase pathway. Also, it showed reversible reaction fluxes of two reactions involved in acetate formation (ACKr/PTAr), thereby impacting acetate levels. In addition, metabolic interactions including amino acid (e.g., arginine, serine, threonine) and mannitol exchange were identified, reflecting both cooperative and competitive features of mixed fermentation. Collectively, this work provides the first comprehensive depiction of the transcriptional and metabolic interplay between S. cerevisiae and O. oeni during mixed fermentation, offering mechanistic insights into microbial cooperation and strategies for the rational design of wine fermentation and flavor quality.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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