娄春波,杜沛,孟凡康,季翔宇,张益豪.人工基因线路的研究进展和未来挑战[J].中国科学院院刊,2018,33(11):1158-1165.

人工基因线路的研究进展和未来挑战

Development and Challenges of Synthetic Genetic Circuits

娄春波
中国科学院微生物研究所 北京 100101
LOU Chunbo
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
杜沛
中国科学院微生物研究所 北京 100101
DU Pei
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
孟凡康
中国科学院微生物研究所 北京 100101
MENG Fankang
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
季翔宇
中国科学院微生物研究所 北京 100101
JI Xiangyu
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
张益豪
北京大学 北京 100871
ZHANG Yihao
Peking University, Beijing 100871, China

         合成生物学;人工基因线路;重编程;环境适应;模块化

        synthetic biology;synthetic genetic circuit;reprogramming;environment adaptation;modularization

        基因线路是生命体对自身生命过程控制的动态调控系统。在工程化的设计原理的指导下，人工基因线路是对天然基因调控线路进行简单化处理和重新编程，以及引入自然界不存在的人造法则。人工基因线路由遗传开关、生物振荡器、逻辑门等组成，以执行诸多调控功能。多种多样的人工基因线路设计与构建，不仅极大地促进了人们对生命调控基本规律的认识，也进一步丰富了人们对天然的生物系统进行改造、再创的手段，并为医药健康、农业环境和工业发酵等领域的实际需求提供了全新解决方案。虽然在过去20年里，人们在人工基因线路领域取得了丰硕的研究成果，但是细胞体内蕴含着的众多复杂生化反应和信号传导途径，为设计和组装具有更加高级功能的基因线路带来了挑战。相应地，如何实现微小细胞内复杂基因线路的可预测设计组装，如何保障基因线路在复杂的体内外环境下发挥稳健的功能，将成为未来几年人工基因线路研究的关键核心问题和势必克服的重大挑战。

        Genetic circuits are dynamic regulation systems that control the life of every living organism. With the principles of engineering, synthetic genetic circuits are designed through simplifying and re-programming natural genetic circuits, and even by creating completely new principles that does not exist in nature. Genetic circuits are consisting of a wide variety of components, including genetic switches, oscillators, logic gates, and so on. The development of diverse synthetic circuits not only facilitated the understanding of basic principles of life, but also enabled the rebuilding of natural biological systems which has provided brand new solutions for a broad range of applications including medicine, agriculture, and industrial fermentation. In the last two decades, the design of synthetic genetic circuits has been seen rapid development, but the complexity of intercellular biochemical reactions and signal transductions still poses great challenges for building genetic circuits with more sophisticated functions. Consequently, the pathways toward predictable assembly in cells of microscopic scale and ensuring reliable circuit performance in complex environments would be major subjects that challenge all researchers in this field.