Using Strand Displacing Polymerase To Program Chemical Reaction Networks
Using Strand Displacing Polymerase To Program Chemical Reaction Networks
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DOI：
10.1021/jacs.0c02240
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发表时间：
2020-05-27
影响因子：
15
通讯作者：
Reif, John
中科院分区：
文献类型：
--
作者：
Shah, Shalin;Wee, Jasmine;Reif, John
化学反应网络（crn）提供了一个强大的抽象形式来表示复杂的生化过程。由于DNA的可编程特性，它为实现crn的抽象表示（或编程语言）提供了一个有希望的基础。先前使用DNA实现crn的工作要么使用纯DNA系统，要么使用多酶DNA电路。只有dna组件的体系结构具有生物学上简单的系统的基本原理。另一方面，多酶系统旨在利用天然酶来提高电路性能，但代价是增加了复杂性。在这项工作中，我们探索了一种替代架构，它位于DNA系统和多酶DNA系统之间的光谱。我们的结构仅依赖于一条链置换聚合酶和DNA杂交反应来实现crn。首先，我们简要介绍了简单crn的理论和DNA设计，然后探讨了基于聚合酶的链位移系统的基本特性。最后，我们在体外设计一个催化放大器作为我们框架的用例，因为这样的放大器需要DNA序列和反应条件的复杂设计。
Chemical reaction networks (CRNs) provide a powerful abstraction to formally represent complex biochemical processes. DNA provides a promising substrate to implement the abstract representation (or programming language) of CRNs due to its programmable nature. Prior works that used DNA to implement CRNs either used DNA-only systems or multienzyme DNA circuits. Architectures with DNA-only components had the rationale of being biologically simple systems. Multienzyme systems, on the other hand, aimed at using natural enzymes to improve circuit performance, although, at the cost of increased complexity. In this work, we explore an alternative architecture that lies along the spectrum in between DNA-only systems and multienzyme DNA systems. Our architecture relies on only a strand displacing polymerase enzyme and DNA hybridization reactions for implementing CRNs. First, we briefly introduce the theory and DNA design of simple CRNs and then explore the fundamental properties of polymerase-based strand displacement systems. Finally, we engineer a catalytic amplifier in vitro as a use-case of our framework since such amplifiers require the intricate design of DNA sequences and reaction conditions.