Quorum Sensing-Based Dual-Function Switch and Its Application in Solving Two Key Metabolic Engineering Problems

被引:47
作者
Gu, Fei [1 ]
Jiang, Wei [1 ]
Mu, Yunlan [1 ]
Huang, Hao [1 ]
Su, Tianyuan [1 ]
Luo, Yue [1 ]
Liang, Quanfeng [1 ]
Qi, Qingsheng [1 ]
机构
[1] Shandong Univ, Qingdao, Peoples R China
来源
ACS SYNTHETIC BIOLOGY | 2020年 / 9卷 / 02期
基金
中国国家自然科学基金;
关键词
dynamic regulation; quorum sensing; metabolic engineering; Esa system; QS switches; DYNAMIC PATHWAY REGULATION; 5-AMINOLEVULINIC ACID; ESCHERICHIA-COLI; REGULATOR; BACTERIA; ESAR; BIOSYNTHESIS; STRATEGIES; STEWARTII; VIABILITY;
D O I
10.1021/acssynbio.9b00290
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Metabolic engineering aims to achieve high yields of desired products. The most common strategies focus on optimization of metabolic flux distributions. The dynamic activation or inhibition of gene expression through quorum sensing (QS) has been applied to metabolic engineering. In this study, we designed and constructed a series of QS-based bifunctional dynamic switches (QS switches) capable of synchronizing the up-regulation and down-regulation of genes at different times and intervals. The bifunctional QS switches were based on the Esa QS system, because EsaR regulatory proteins can act as transcriptional activator and repressor. The QS switches' effectiveness and feasibility were verified through fluorescence characterization. Finally, the QS switches were applied to the production of 5-aminolevulinic acid (ALA) and poly-beta-hydroxybutyrate (PHB) to solve two key metabolic engineering problems: necessary gene knockout and redirection of metabolic flux. The production of PHB and ALA was increased 6- and 12-fold in Escherichia coli, respectively.
引用
收藏
页码:209 / 217
页数:17
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