Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5600 MB Eindhoven, The Netherlands.
Nat Chem. 2015 Feb;7(2):160-5. doi: 10.1038/nchem.2142. Epub 2015 Jan 12.
Life is sustained by complex systems operating far from equilibrium and consisting of a multitude of enzymatic reaction networks. The operating principles of biology's regulatory networks are known, but the in vitro assembly of out-of-equilibrium enzymatic reaction networks has proved challenging, limiting the development of synthetic systems showing autonomous behaviour. Here, we present a strategy for the rational design of programmable functional reaction networks that exhibit dynamic behaviour. We demonstrate that a network built around autoactivation and delayed negative feedback of the enzyme trypsin is capable of producing sustained oscillating concentrations of active trypsin for over 65 h. Other functions, such as amplification, analog-to-digital conversion and periodic control over equilibrium systems, are obtained by linking multiple network modules in microfluidic flow reactors. The methodology developed here provides a general framework to construct dissipative, tunable and robust (bio)chemical reaction networks.
生命是由远离平衡状态的复杂系统维持的，这些系统由众多酶反应网络组成。生物学调控网络的工作原理是已知的，但体外组装非平衡酶反应网络一直具有挑战性，这限制了表现出自主动力的合成系统的发展。在这里，我们提出了一种理性设计具有动态行为的可编程功能反应网络的策略。我们证明，一个围绕酶胰蛋白酶的自动激活和延迟负反馈构建的网络能够产生持续振荡的活性胰蛋白酶浓度超过 65 小时。通过在微流控流动反应器中连接多个网络模块，可以获得其他功能，如放大、模数转换和对平衡系统的周期性控制。这里开发的方法为构建耗散、可调谐且稳健的（生物）化学反应网络提供了一个通用框架。
