Department of Bioengineering, University of California-San Diego, La Jolla, CA, USA.
BioCircuits Institute, University of California-San Diego, La Jolla, CA, USA.
Science. 2019 Sep 6;365(6457):1045-1049. doi: 10.1126/science.aaw0542.
Advances in synthetic biology have led to an arsenal of proof-of-principle bacterial circuits that can be leveraged for applications ranging from therapeutics to bioproduction. A unifying challenge for most applications is the presence of selective pressures that lead to high mutation rates for engineered bacteria. A common strategy is to develop cloning technologies aimed at increasing the fixation time for deleterious mutations in single cells. We adopt a complementary approach that is guided by ecological interactions, whereby cyclical population control is engineered to stabilize the functionality of intracellular gene circuits. Three strains of were designed such that each strain could kill or be killed by one of the other two strains. The resulting "rock-paper-scissors" dynamic demonstrates rapid cycling of strains in microfluidic devices and leads to an increase in the stability of gene circuit functionality in cell culture.
合成生物学的进步带来了一系列原理验证的细菌回路，可以应用于从治疗到生物生产的各种领域。对于大多数应用来说，一个普遍的挑战是存在选择压力，导致工程细菌的突变率很高。一种常见的策略是开发克隆技术，旨在增加单个细胞中有害突变的固定时间。我们采用了一种互补的方法，该方法受生态相互作用的指导，通过循环的种群控制来稳定细胞内基因回路的功能。设计了三种 菌株，使得每种菌株都可以被另外两种菌株中的一种杀死或杀死。由此产生的“石头剪刀布”动态展示了在微流控设备中菌株的快速循环，并导致细胞培养中基因回路功能的稳定性提高。
