Applications of toxin-antitoxin systems in synthetic biology

Jianzhong Lin , Yunxue Guo , Jianyun Yao , Kaihao Tang , Xiaoxue Wang
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引用次数: 5

Abstract

Toxin-antitoxin (TA) systems are ubiquitous in bacteria and archaea. Most are composed of two neighboring genetic elements, a stable toxin capable of inhibiting crucial cellular processes, including replication, transcription, translation, cell division and membrane integrity, and an unstable antitoxin to counteract the toxicity of the toxin. Many new discoveries regarding the biochemical properties of the toxin and antitoxin components have been made since the first TA system was reported nearly four decades ago. The physiological functions of TA systems have been hotly debated in recent decades, and it is now increasingly clear that TA systems are important immune systems in prokaryotes. In addition to being involved in biofilm formation and persister cell formation, these modules are antiphage defense systems and provide host defenses against various phage infections via abortive infection. In this review, we explore the potential applications of TA systems based on the recent progress made in elucidating TA functions. We first describe the most recent classification of TA systems and then introduce the biochemical functions of toxins and antitoxins, respectively. Finally, we primarily focus on and devote considerable space to the application of TA complexes in synthetic biology.

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毒素-抗毒素系统在合成生物学中的应用
毒素-抗毒素(TA)系统在细菌和古细菌中普遍存在。它们大多由两个相邻的遗传元素组成,一个是稳定的毒素,能够抑制关键的细胞过程,包括复制、转录、翻译、细胞分裂和膜完整性,另一个是不稳定的抗毒素,可以抵消毒素的毒性。自从近40年前第一个TA系统被报道以来,关于毒素和抗毒素成分的生化特性有了许多新的发现。近几十年来,TA系统的生理功能一直备受争议,现在越来越清楚TA系统是原核生物中重要的免疫系统。除了参与生物膜的形成和持久性细胞的形成外,这些模块是噬菌体防御系统,并通过流产感染为宿主提供各种噬菌体感染的防御。在本文中,我们基于近年来研究TA功能的进展,探讨了TA系统的潜在应用。我们首先描述了TA系统的最新分类,然后分别介绍了毒素和抗毒素的生化功能。最后,我们主要关注TA配合物在合成生物学中的应用,并投入了相当大的篇幅。
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