关键词: 动态调控, 代谢物响应, 群体感应, 环境响应, 代谢工程, 蛋白水平调控

Abstract:

As a sustainable biochemical reactor, microbial cell factories are widely used in the production of value-added compounds such as natural products, pharmaceuticals and nutraceuticals. In order to make microbial cell factories produce target compounds with high titer, productivity and yield, metabolic engineering strategies are employed to rationally modify and regulate their metabolism. However, knockout and overexpression of genes inevitably bring stresses such as redox imbalance and toxic intermediate accumulation. While dynamic control strategy has been proven as a promising tool to address these challenges by balancing carbon flux and energy generation and dissipation for cell growth and generation of target compounds. As a result, many dynamic regulation elements and gene circuits have been developed and widely used in metabolic engineering so far. In this review, we summarize four types of attractive dynamic regulation systems based on metabolite-response, quorum sensing-response, environmental parameter-response and protein level regulation, with a focus on the construction method of various regulatory elements and their applications in metabolic engineering. In addition, challenges faced by different dynamic control strategies in industrial applications are analyzed. At the same time, we prospect the application potentials of some strategies such as high-throughput screening, protein engineering, computer simulation and mathematical model analysis coupled with gene control elements in solving the problems of narrow response threshold and limited control range of dynamic regulation tools. With the further development of synthetic biology and metabolic engineering, we believe that dynamic control strategy will be widely used for the construction of microbial cell factories in the near future.

Key words: dynamic regulation, metabolite-response, quorum sensing, environmental parameter-response, metabolic engineering, protein level regulation