文献类型： 外文期刊

作者： Kato, Yusuke ¹ ; Mori, Hirotada ² ;

作者机构： 1.Natl Agr & Food Res Org NARO, Inst Agrobiol Sci, Tsukuba, Ibaraki, Japan

2.Nara Inst Sci & Technol, Data Sci Ctr, Lab Syst Microbiol, Ikoma, Nara, Japan

3.Guangdong Acad Agr Sci, Inst Anim Sci, Innovat Lab Syst Microbiol & Synthet Biol, Guangzhou, Guangdong, Peoples R China

关键词： genetic stability; biological containment; toxic overexpression; genetic devices; ASKA library

期刊名称：FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY （ 影响因子：5.7； 五年影响因子：6.2 ）

ISSN： 2296-4185

年卷期： 2024 年 12 卷

页码：

收录情况： SCI

摘要： Genetic instability of synthetic genetic devices is a key obstacle for practical use. This problem is particularly critical in kill-switches for conditional host killing. Here, we propose a genetically stable kill-switch based on a "demon and angel" expression construct of a toxic essential gene. The kill-switch conditionally overexpresses the toxic essential gene. Additionally, the identical essential gene is deleted in the genome. The essential gene is expressed at a low level to maintain host survival in the OFF state and kills the host by the overexpression in the ON state. The single expression construct is responsible for both killing the hosts and maintaining viability, reducing the emergence of loss-of-function mutants. We constructed the kill-switch using the toxic essential gene encoding tyrosyl-tRNA synthetase, tyrS, in Escherichia coli. The bacteria harboring the kill-switch were conditionally suicidal over 300 generations. Toxic overexpression of essential genes has also been found in other organisms, suggesting that the "demon and angel" kill switch is scalable to various organisms.