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Comparative metabolic profiling of engineered Saccharomyces cerevisiae with enhanced flavonoids production
Journal of Functional Foods ( IF 3.8 ) Pub Date : 2018-03-23 , DOI: 10.1016/j.jff.2018.03.012
Xiaomei Lyu , Kuan Rei Ng , Rita Mark , Jie Lin Lee , Wei Ning Chen

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.



中文翻译:

工程化酿酒酵母具有增强的类黄酮生成的比较代谢谱分析

工程酿酒酵母先前显示具有ARO4K229L过表达,PHA2下调和ARO10 / PDC5敲除的菌株具有增强的柚皮苷积累。为了了解其背后的机制,进行了比较代谢组学分析,以全面了解代谢调节。结果,发现20种重要的代谢物发生了显着变化。具体而言,ARO4K229L的过表达导致细胞质氨基酸产生的减少和NADPH水平的增加。这表明糖酵解途径下调,而PPP途径上调。在PHA2-下调的菌株中,代谢变化主要局限于类黄酮的生物合成途径。如果是ARO10 / PDC5敲除菌株,观察到TCA周期中ATP水平显着提高和上调。这些结果为芳香醇在新陈代谢水平上的呼吸抑制提供了新的证据。体内基因工程。

更新日期:2018-03-23
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