调控工程在光合蓝细菌中的应用  

Applications of regulatory engineering in photosynthetic cyanobacteria

作　　者：董正鑫 孙韬[1,2,4] 陈磊 张卫文[1,2,3,4,5] DONG Zhengxin;SUN Tao;CHEN Lei;ZHANG Weiwen(Laboratory of Synthetic Microbiology,School of Chemical Engineering&Technology,Tianjin University,Tianjin 300072,China;Center for Biosafety Research and Strategy,Tianjin University,Tianjin 300072,China;Key Laboratory of Systems Bioengineering,Ministry of Education of China,Tianjin 300072,China;Frontier Science Center for Synthetic Biology,Ministry of Education of China,Tianjin 300072,China;Collaborative Innovation Center of Chemical Science and Engineering,Tianjin 300072,China)

机构地区：[1]天津大学化工学院合成微生物学实验室,天津300072 [2]天津大学生物安全战略研究中心,天津300072 [3]教育部系统生物工程重点实验室,天津300072 [4]教育部合成生物学前沿科学中心,天津300072 [5]化学化工协同创新中心,天津300072

出　　处：《合成生物学》2022年第5期966-984,共19页Synthetic Biology Journal

基　　金：国家重点研发计划(2018YFA0903000,2019YFA0904600,2018YFA0903600)。

摘　　要：能源短缺与环境污染问题限制着人类发展,光合蓝细菌因能够利用太阳能将CO固定生成燃料和化学品而受到广泛关注。迄今为止,在光合蓝细菌中已实现近百种燃料和化学品由CO的生物合成,有望促进CO的资源化利用并助力“碳中和”。调控工程能够实现基因表达多层次调控及代谢网络的全局性调控,是提高光合蓝细菌CO固定效率的有效手段。本文首先归纳了光合蓝细菌底盘中的双组分信号转导系统、调控小RNA和σ因子等3种主要调控系统的分类、作用过程以及功能;介绍了光合蓝细菌调控系统中的调控元件功能研究,系统总结了光合蓝细菌中通过调控系统元件改造,提高底盘鲁棒性、优化产品生产所进行的调控工程;最后,讨论了光合蓝细菌中调控工程的未来研究方向,重点包括调控系统功能阐明、工具开发、多基因调控、调控系统蛋白工程改造和系统调控工程等。总之,有望通过系统调控工程,实现对光合蓝细菌底盘细胞全局代谢网络的精确调控。Energy shortage and environmental pollution are the limiting factors for the development of human society.Photosynthetic cyanobacteria have attracted increasing attention due to their ability to use solar energy for the fixation of COfor green production of biofuels and chemicals under low nutrient conditions.So far,nearly 100 kinds of fuels and chemicals have been synthesized in photosynthetic cyanobacteria directly from CO,which is expected topromote COutilization and contribute to“carbon neutrality”.However,the industrial applications of photosynthetic cyanobacteria are restricted by factors such as their slow growth rate,low biomass,low product yield,and poor environmental robustness.Regulatory engineering,enabling global regulation of metabolic networks and multi-level regulation of genes expression,is a powerful tool to address these challenges.In this paper,we firstly introduce the classification,mechanism,and function of three major regulatory systems,including two-component signal transduction systems(TCS),regulatory small RNAs(s RNAs),andσfactor in photosynthetic cyanobacteria.Subsequently,we briefly discuss the functions of regulatory elements in the regulatory systems of photosynthetic cyanobacteria related to the tolerance against high salt,short-chain alcohols,light stress,metal ions,oxidative stress,as well as heat and drought,and the regulation of carbon metabolism in the production of the target components.We systematically review the applications of regulatory engineering,based on engineered regulatory system elements,in improving the robustness of photosynthetic cyanobacteria under the above stress conditions and in optimizing the carbon fluxes towards product biosynthesis.Finally,we conclude with the future research focuses of regulatory engineering in photosynthetic cyanobacteria,highlighting research areas such as functional elucidation of the regulatory systems,toolbox development,multi-gene regulations,protein engineering of the regulatory systems,and systematic regulatory engineering

关 键 词：光合蓝细菌 自养型细胞工厂 碳中和 调控工程 双组分系统 小RNA Σ因子 

分 类 号：Q819[生物学—生物工程]