Transcriptome analysis and reverse engineering verification of SNZ3 Val125Ile and Pho3 Asn134Asp revealed the mechanism of laboratory adaptive evolution to increase the yield of tyrosol in Saccharomyces cerevisiae S26

Background Tyrosol is an important drug precursor, and Saccharomyces cerevisiae is one of the main microorganisms producing tyrosol. Although excessive metabolic modification increased the production of tyrosol, it also caused a decrease in the growth rate of yeast. Therefore, this study attempted to restore the growth of S. cerevisiae through adaptive evolution and further improve tyrosol production. Results After the adaptive laboratory evolution of S. cerevisiae S26, three evolutionary strains were obtained. The biomass of strain S26-AE2 reached 17.82 under the condition of 100 g/L glucose which was 15.33% higher than that of S26, and its tyrosol production reached 817.83 mg/L. Transcriptome analysis showed that the strain S26-AE2 may through decreased expression of HXK2 reduce the transcriptional regulation of glucose repression and increase the expression of gene PGI1 to promote the utilization of glucose. The genes related to pyruvate synthesis were enhanced in strain S26-AE2. Under the 20 g/L glucose condition, the TCA cycle-related genes of the S26-AE2 were more active. Furthermore, the tyrosol production of S26 with SNZ3^Val125Ile mutation increased by 17.01% compared with the control strain S26 under the condition of 100 g/L glucose. Conclusions In this paper, a strain S26-AE2 with good growth and tyrosol production performance was obtained by adaptive evolution. The transcriptome reveals the differences in gene expression in metabolic pathways of adaptive evolutionary strains may be related to the growth of yeast and the production of tyrosol. Further reverse engineering verified the mutation of SNZ3 promoted the synthesis of tyrosol in S. cerevisiae in the glucose-rich medium. This study provides a theoretical basis for the metabolic engineering of S. cerevisiae to synthesize tyrosol and its derivatives.