Synthetic Biology Journal ›› 2024, Vol. 5 ›› Issue (1): 38-52.DOI: 10.12211/2096-8280.2023-016

• Invited Review • Previous Articles     Next Articles

Research progress in biosensors based on bacterial two-component systems

Jingyu ZHAO, Jian ZHANG, Qingsheng QI, Qian WANG   

  1. National Glycoengineeing Research Center,State Key Laboratory of Microbial Technology,Shandong University,Qingdao 266237,Shandong,China
  • Received:2023-02-22 Revised:2023-07-01 Online:2024-03-20 Published:2024-02-29
  • Contact: Qingsheng QI, Qian WANG

基于细菌双组分系统的生物传感器的研究进展

赵静宇, 张健, 祁庆生, 王倩   

  1. 山东大学,国家糖工程技术研究中心,微生物技术国家重点实验室,山东 青岛 266237
  • 通讯作者: 祁庆生,王倩
  • 作者简介:赵静宇(1998—),女,硕士研究生。研究方向为微生物代谢工程与合成生物学。 E-mail:1504362801@qq.com
    祁庆生(1966—),男,教授,山东大学微生物技术国家重点实验室副主任。研究方向为代谢工程与合成生物学,废弃塑料降解及生物可降解塑料的合成等。 E-mail:qiqingsheng@sdu.edu.cn
    王倩(1983—),女,博士,教授。研究方向为微生物代谢工程与合成生物学。 E-mail:qiqi20011983@gmail.com
  • 基金资助:
    国家重点研发计划“合成生物学专项”(2019YFA0904900);国家自然科学基金面上项目(32270089)

Abstract:

Two-component systems (TCSs) in bacteria, are capable of sensing and making responses to physical, chemical, and biological stimuli within and outside the cells, and subsequently induce a wide range of cellular processes through the role played by the regulatory component and the response component in combination, which is a ubiquitous signal transduction pathway. At present, an growing number of synthetic biologists have devoted their effort to using the specific and irreplaceable properties of TCSs to design biosensors with the aim of applying in optogenetics, materials science, engineering of gut microbiome, biorefining and soil improvement, and the like. The purpose of this review is to focus on the most recent research advances in the development of biosensors based on TCSs and their potential applications. At the same time, topics of great importance are discussed on how to use novel engineering methods with synthetic biology to improve the reliability and robustness of the performance of the biosensors, such as genetic remodeling, DNA-binding domain swapping, tuning of the detection threshold and isolation of phosphorylation crosstalk as well as on how to customize the signal characteristics of TCSs to meet particular needs according to the requirements of specific applications. It would be possible in the future for scientists to combine these methods with gene synthesis on a large scale and high-throughput screening in order to speed up and give synthetic biologists a hand in the discovery of TCSs with numerous uncharacterized signal inputs and the development of genetically encoded novel biosensors that may be capable of responding to a broad range of stimuli. This allows for extending the applications of the biosensors in different fields.

Key words: synthetic biology, two-component systems, whole-cell biosensors, metabolic engineering, optogenetics, bacterial diagnostics

摘要:

细菌双组分系统能够感知和响应细胞内外的物理、化学和生物刺激,通过耦合传感和调节机制从而引起一系列的细胞反应,是一个普遍存在的信号转导通路家族。当前越来越多的合成生物学家已开始利用双组分系统的特异属性来工程化设计微生物传感系统,并应用于光遗传学、材料科学、肠道微生物组工程、生物炼制和土壤改良等领域。本综述重点介绍了开发基于双组分系统的生物传感器的最新研究进展以及在各个领域中的潜在应用。同时探讨了如何运用新的工程方法提高双组分系统传感器性能的可靠性,包括遗传重构、DNA结合结构域交换、检测阈值调节和磷酸化串扰隔离,以及如何根据特定应用的要求定制双组分系统信号特性。在未来,研究者可以将这些方法与大规模的基因合成、高通量筛选相结合,以加速和帮助发现更多未确定特征输入的双组分系统,并开发新的对广泛的刺激做出反应的基因编码生物传感器,拓展双组分生物传感器在不同领域的应用。

关键词: 合成生物学, 双组分系统, 细胞生物传感器, 代谢工程, 光遗传学, 细菌诊断

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