核糖核酸开关用于微生物细胞工厂的智能与精细调控

Intelligent and fine regulation of microbial cell factory based on riboswitches

利用代谢工程与合成生物技术对细胞内复杂的代谢网络和调控网络进行重构和改造,以建立合成新化合物或提高目标产物产量的微生物细胞工厂是当今绿色化工技术发展的方向之一。微生物代谢途径的调控受环境和遗传的双重影响,细胞通过全局转录因子、信使分子和反馈抑制等方式响应环境变化来维持细胞的内稳态;同时细胞还受自身遗传基因线路的调控,在转录、翻译以及翻译后修饰过程中调控特定基因的表达。核糖核酸开关是一类调控基因线路表达的RNA元件,通过与金属离子、糖类衍生物、氨基酸、核酸衍生物以及辅酶等特异性配体结合发生的构象变化,从而启动或阻断m RNA的转录、翻译、拼接等过程来调控基因的表达。核糖核酸开关作为天然的生物感受器和效应器通过人工设计可成为微生物细胞工厂智能化和精细化调控的分子工具,并在化工、医药、环保、食品等领域得到广泛应用。

Construction of the microbial cell factory is one of the developmental directions of current green chemical industry. The microbial cell factory is a kind of recombined microorganism and its metabolic and regulatory pathways have been reconstructed by metabolic engineering and synthetic biology to synthetic new compounds or to improve the yield of target production. The microbial metabolic pathway is regulated by two points： environment and genetic information. The cell maintains its homeostasis by global transcription factors, messenger molecules and feedback inhibition when the circumstance is changed. Meanwhile, the cell is affected by its own genetic circulate through transcription, translation and post-translational modification to regulate the expression of target gene. The riboswitches are RNA elements which change their conformation when bind to specific ligands such as ions, sugar derivatives, amino acids, nucleic acid derivatives and coenzymes to regulate the process of transcription, translation and splicing of mRNA. The riboswitches are natural biosensors and bioeffectors which can be designed as the intelligent molecular tools to fine regulate microbial cell factories. Using riboswitches in the microbial cell factory can extend the application in the field of chemical, pharmaceutical, environmental protection and food production.