Comparative metabolic profiling of engineered Saccharomyces cerevisiae with enhanced flavonoids production

The engineered Saccharomyces cerevisiae strains with ARO4K229L-overexpression, PHA2-downregulation and ARO10/PDC5-knockouts, were previously shown to have enhanced accumulation of naringenin. To understand the mechanism behind this, comparative metabolomic analysis was performed, to gain a global overview of the metabolic regulation. As a result, 20 important metabolites were found to be significantly altered. Specifically, the overexpression of ARO4K229L resulted in a decrease in cytoplasmic amino acids production and an increase in NADPH levels. This indicated that there was a downregulation of the glycolysis pathway, combined with an upregulation in the PPP pathway. In the PHA2-down regulated strain, metabolic changes were mainly confined to the flavonoid biosynthetic pathway. In the case of the ARO10/PDC5 knockout strain, significantly improved ATP levels and upregulation in the TCA cycle were observed. These results provided new evidence for the respiration inhibition of aromatic alcohol at the metabolic level, as a result of in vivo genetic engineering.