Unveiling the mechanism of efficient β‐phenylethyl alcohol conversion in wild‐type Saccharomyces cerevisiae WY319 through multi‐omics analysis

Abstract β‐Phenylethanol (2‐PE), as an important flavor component in wine, is widely used in the fields of flavor chemistry and food health. 2‐PE can be sustainably produced through Saccharomyces cerevisiae . Although significant progress has been made in obtaining high‐yield strains, as well as improving the synthesis pathways of 2‐PE, there still lies a gap between these two fields to unpin. In this study, the macroscopic metabolic characteristics of high‐yield and low‐yield 2‐PE strains were systematically compared and analyzed. The results indicated that the production potential of the high‐yield strain might be contributed to the enhancement of respiratory metabolism and the high tolerance to 2‐PE. Furthermore, this hypothesis was confirmed through comparative genomics. Meanwhile, transcriptome analysis at key specific growth rates revealed that the collective upregulation of mitochondrial functional gene clusters plays a more prominent role in the production process of 2‐PE. Finally, findings from untargeted metabolomics suggested that by enhancing respiratory metabolism and reducing the Crabtree effect, the accumulation of metabolites resisting high 2‐PE stress was observed, such as intracellular amino acids and purines. Hence, this strategy provided a richer supply of precursors and cofactors, effectively promoting the synthesis of 2‐PE. In short, this study provides a bridge for studying the metabolic mechanism of high‐yield 2‐PE strains with the subsequent targeted strengthening of relevant synthetic pathways. It also provides insights for the synthesis of nonalcoholic products in S. cerevisiae .