The application of biological reverse engineering in synthetic biology

doi:10.12211/2096-8280.2020-063

Abstract

Abstract:

Aiming to purposefully and rationally design and construct predictable man-made life systems with pre-defined functions under the guidance of engineering principles, synthetic biology is an advanced interdisciplinary science by combining a broad range of methodologies from various disciplines, such as traditional biology, bioengineering, systems biology, mathematics, physics, chemistry, and information science. With the booming development for nearly two decades, great progress has been made in synthetic biology. However, there are a number of factors that should be taken into account for rationally designing complex systems, such as robustness and bifurcation. Because of the consistency between the research idea of biological reverse engineering and the design process of synthetic biology, we are enlightened to resolve these problems in rationally designing genetic circuits with compley pre-defined functions with the help of reverse engineering In this review, based on the accumulated experience of our research group in reverse engineering, we started with engineering principles and design difficulties in synthetic biology, and then summarized the current methods of applying reverse engineering in synthetic biology, including network enumeration, sub-network combinations, the method from Boolean network model to continuous model. In addition, we proved the efficiency of combining reverse engineering with synthetic biology to rationally design biological complex regulation networks. Finally, we concluded with the analysis of bottlenecks for the application of reverse engineering in synthetic biology.

Key words: reverse engineering, synthetic biology, rational design, Boolean network, network enumeration

摘要：

合成生物学是一门涉及生物学、生物工程学、系统生物学、数学、物理、化学与信息科学的新生的交叉学科。它的目的是在工程化思想的指导下有目的地、可预测地设计人造生命系统。经过近二十年的蓬勃发展，合成生物学取得了重大成就，但依旧面临复杂系统理性设计的困难。在系统生物学中，运用数学物理等知识根据网络功能来研究功能背后网络结构的方法被称为逆向工程。系统生物学逆向工程的研究思路与合成生物学设计过程的一致性，启发了我们利用逆向工程指导合成生物学的理性设计。逆向工程应用到合成生物学，将大大降低复杂功能回路的设计难度。本文从合成生物学的设计思路与问题出发，根据本文作者研究团队近十年来在逆向工程研究中的经验，归纳总结了目前逆向工程设计在合成生物学中的应用方法，包括网络穷举方法、子网络拼接方法、从离散模型到连续模型的方法，论证了逆向工程指导合成生物学理性设计的可行性与有效性，分析了目前逆向工程设计在合成生物学中的发展瓶颈。

关键词: 逆向工程, 合成生物学, 理性设计, 布尔网络, 网络穷举

CLC Number:

Xinmao CHEN, Qi OUYANG. The application of biological reverse engineering in synthetic biology[J]. Synthetic Biology Journal, 2020, 1(1): 29-43.

陈欣懋, 欧阳颀. 生物逆向工程设计在合成生物学中的应用[J]. 合成生物学, 2020, 1(1): 29-43.

Figures/Tables 18

References 60

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