Abstract:

Metabolic engineering is a key technology for the biosynthesis of various bio-based products such as nutraceuticals, pharmaceuticals, biofuels, and chemicals through the design, construction and optimization of metabolic pathways. Traditional methods, including gene knockout, gene knockdown and gene overexpression usually lead to metabolic imbalance. In contrast, using the regulatory elements derived from the microorganisms themselves to carry out dynamic regulation of metabolic pathways can balance the cell growth and product synthesis, achieving unification of high titer, high yield and high productivity. Microorganisms have the ability to alter their metabolic flux in transcription level by sensing the exchange of environment or intracellular metabolite concentration, and can change the metabolic state using some cis-or trans-regulation elements in post-transcription level, besides allosteric regulation and controlled degradation of pathway enzymes are found in protein level. Dynamic regulation elements can be developed basing on these regulatory mechanisms and can be applied into the dynamic regulation of microbial metabolic. We summarize the dynamic regulation elements in transcription, post-transcription and protein levels respectively, and introduce their applications in microbial metabolic engineering.

Key words: metabolism engineering, regulation elements, synthetic biology, dynamic regulation, biotechnology, biochemical engineering

摘要：

代谢工程是通过对代谢途径的设计、构建与优化，进行营养品、药品、生物燃料以及化工产品等各种生物基产品合成的关键技术。传统的改造策略如基因的敲除、弱化与过表达会造成代谢流的失衡，而利用微生物自身的调控方式和调控元件，构建合成调控元件，对代谢途径进行动态调控，可以平衡细胞生长与产物合成，从而实现高产量、高底物转化率与高生产强度的统一。利用微生物在转录水平对于外界环境以及胞内代谢物浓度的变化的响应机制，以及在转录后水平通过顺式及反式作用元件的调控，和在蛋白质水平通过途径酶的别构调节以及对蛋白质降解速率的调节，都能开发出相应的动态调控元件并对微生物的代谢进行动态调控。本文分别从转录水平、转录后水平及蛋白质水平3个层次总结了目前常见的一些动态调控元件，并对其在微生物代谢工程中的应用进行了介绍。

关键词: 代谢工程, 调控元件, 合成生物学, 动态调控, 生物技术, 生化工程