Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
Biotechnol Adv. 2019 Nov 1;37(6):107393. doi: 10.1016/j.biotechadv.2019.04.015. Epub 2019 Apr 30.
Living organisms evolve complex genetic networks to interact with the environment. Due to the rapid development of synthetic biology, various modularized genetic parts and units have been identified from these networks. They have been employed to construct synthetic genetic circuits, including toggle switches, oscillators, feedback loops and Boolean logic gates. Building on these circuits, complex genetic machines with capabilities in programmable decision-making could be created. Consequently, these accomplishments have led to novel applications, such as dynamic and autonomous modulation of metabolic networks, directed evolution of biological units, remote and targeted diagnostics and therapies, as well as biological containment methods to prevent release of engineered microorganisms and genetic materials. Herein, we outline the principles in genetic circuit design that have initiated a new chapter in transforming concepts to realistic applications. The features of modularized building blocks and circuit architecture that facilitate realization of circuits for a variety of novel applications are discussed. Furthermore, recent advances and challenges in employing genetic circuits to impart microorganisms with distinct and programmable functionalities are highlighted. We envision that this review gives new insights into the design of synthetic genetic circuits and offers a guideline for the implementation of different circuits in various aspects of biotechnology and bioengineering.
生物体会进化出复杂的遗传网络来与环境相互作用。由于合成生物学的快速发展，从这些网络中已经鉴定出各种模块化的遗传部件和单元。它们被用于构建合成遗传电路，包括 toggle 开关、振荡器、反馈回路和布尔逻辑门。基于这些电路，可以构建具有可编程决策能力的复杂遗传机器。因此，这些成就带来了新的应用，如代谢网络的动态和自主调节、生物单元的定向进化、远程和靶向诊断和治疗，以及防止工程微生物和遗传物质释放的生物遏制方法。本文概述了遗传电路设计的原理，这些原理开创了将概念转化为现实应用的新篇章。讨论了模块化构建块和电路架构的特点，这些特点有助于实现各种新型应用的电路。此外，还强调了遗传电路在赋予微生物独特和可编程功能方面的最新进展和挑战。我们设想，这篇综述为合成遗传电路的设计提供了新的见解，并为在生物技术和生物工程的各个方面实施不同的电路提供了指导。
