酿酒酵母
代谢组
羟基酪醇
代谢工程
生化工程
限制
代谢途径
生物化学
代谢组学
合成生物学
生物技术
计算生物学
生物信息学
生物
酵母
基因
工程类
多酚
抗氧化剂
机械工程
作者
Yingjie Liu,Bixuan Gu,Jihua Shi,Changchun Fu,Xuepeng Zhang,Xinqi Chen,Ruijin Yang,Xiaomei Lyu
标识
DOI:10.1016/j.biortech.2024.131187
摘要
Metabolic engineering provides a powerful approach to efficiently produce valuable compounds, with the aid of emerging gene editing tools and diverse metabolic regulation strategies. However, apart from the current known biochemical pathway information, a variety of unclear constraints commonly limited the optimization space of cell phenotype. Hydroxytyrosol is an important phenolic compound that serves various industries with prominent health-beneficial properties. In this study, the inverse metabolic engineering based on metabolome analysis was customized and implemented to disclose the hidden rate-limiting steps and thus to improve hydroxytyrosol production in Saccharomyces cerevisiae (S. cerevisiae). The potential rate-limiting steps involved three modules that were eliminated individually via reinforcing and balancing metabolic flow, optimizing cofactor supply, and weakening the competitive pathways. Ultimately, a 118.53 % improvement in hydroxytyrosol production (639.84 mg/L) was achieved by inverse metabolic engineering.
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