Integrative multi-omics reveals genetic and transcriptomic determinants of aroma formation during alcoholic fermentation in Saccharomyces cerevisiae

Aroma-active volatile organic compounds (VOCs) produced during alcoholic fermentation by Saccharomyces cerevisiae are key determinants of the sensory quality of fermented beverages. However, the molecular mechanisms underlying strain-specific aroma diversity remain incompletely understood. Thus, this study aimed to integrate genomic, transcriptomic, and metabolomic analyses to elucidate the genetic and regulatory determinants of VOC biosynthesis in three S. cerevisiae strains. Whole-genome sequencing identified genomic variation among strains, whereas RNA sequencing (RNA-seq) analyses revealed distinct transcriptional profiles among the strains. Gas chromatography–mass spectrometry (GC–MS) profiling identified strain-dependent differences in VOC composition, including higher alcohols, esters, and acids. Integrative analysis demonstrated that elevated expression of ADH1 , ADH3 , and ADH5 in strain SC8292 was associated with production of higher alcohols via the Ehrlich pathway, whereas upregulation of EEB1 and EHT1 promoted fatty acid ester synthesis. In contrast, strain SC8293 showed strong expression of ADH2 and PDC1 , which coincided with acetaldehyde accumulation, whereas strain SC8301 was enriched in acetate esters, contributing to fruity aromas. Gene synteny analysis revealed the absence of ALD2 in SC8292, explaining the lack of acetic acid production in this strain. Furthermore, transcription factors including GCR1, ADR1, and SIP4 were implicated in regulating VOC biosynthesis. Collectively, these findings demonstrate that genomic variation and transcriptional regulation jointly shape strain-specific aroma profiles. The integration of multi-omics datasets provides mechanistic insight into the molecular basis of aroma diversity and identifies candidate targets for strain selection and metabolic engineering to improve fermentation flavor quality.