Abstract:

The production of target products in microbial cell factories will face problems such as nutrient consumption, metabolite accumulation, heterologous pathway pressure and genetic instability, leading to metabolic imbalances. Therefore, it is necessary to redesign the metabolic pathway of cells, so that the metabolic pathway can automatically adjust metabolic flux according to the changes of fermentation conditions and other environmental conditions to achieve efficient production. In this review, the classification, regulatory mechanism and application of dynamic regulatory elements are introduced firstly, and the proteinous transcription factor regulatory elements and RNA ribose switch regulatory elements which interact with inducers or inducing factors are mainly described. Then the design and modification strategies of dynamic regulatory elements based on transcription factors and promoter sequences are introduced. Subsequently, strategies for construction of dynamic regulatory network in metabolic pathway using inducible regulatory elements are summarized. The regulation of gene expression has shifted from single-input signal regulation to multi-input signal logic gate regulation, and a more accurate dynamic regulatory network can be constructed through multiple input signal logic gate and closed-loop metabolite feedback loop. The construction of dynamic regulatory network will be significant for construction of most effective microbial cell factories.

Key words: inducible regulatory element, gene switch, logic gate, feedback loop, dynamic regulatory network

摘要：

微生物细胞工厂生产目标产物时会面临营养物质消耗、代谢物积累、异源途径压力和遗传不稳定等问题，导致代谢失衡，因此需要对细胞代谢途径重新进行设计，使代谢途径根据发酵等环境条件的变化自动调节代谢通量，达到高效生产。本文首先介绍了动态调控元件的主要类型、调控机制及其应用，重点讲述了与诱导物或诱导因素作用的蛋白质转录因子调控元件和RNA核糖开关调控元件；并且从转录因子与启动子序列两个方面介绍了动态调控元件的设计与改造策略；随后总结了诱导调控元件应用于代谢途径动态调控网络构建的策略，基因表达调控已从单输入信号调控转向多输入信号逻辑门调控，通过多重诱导输入信号的逻辑门和闭环代谢物反馈回路构建更精确的动态调控网络。

关键词: 诱导调控元件, 基因开关, 逻辑门, 反馈回路, 动态调控网络