Multiple feedback loop design in the tryptophan regulatory network of Escherichia coli suggests a paradigm for robust regulation of processes in series
Multiple feedback loop design in the tryptophan regulatory network of Escherichia coli suggests a paradigm for robust regulation of processes in series
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DOI：
10.1098/rsif.2005.0103
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发表时间：
2006-06-22
影响因子：
3.9
通讯作者：
Doyle, Francis J., III
中科院分区：
文献类型：
--
作者：
Bhartiya, Sharad;Chaudhary, Nikhil;Doyle, Francis J., III
生物网络通过适应不确定的环境而进化。在不同的可能的设计范例中，有些可能比其他的提供功能上的优势。这些设计可以通过分子相互作用产生的网络结构和参数值来量化。因此，人们可能喜欢识别进化网络中存在的设计主题，使其优于其他选择。在这项工作中，我们重点研究了以序列排列过程为特征的调节网络，这些过程由多个反馈回路调节。具体来说，我们考虑大肠杆菌中存在的色氨酸系统，它可以被概念化为三个系列过程，即转录、翻译和色氨酸合成。多反馈环基序由遗传抑制、mRNA衰减和酶抑制三个不同的负反馈环产生。介绍了一个框架，以确定该网络负责其生理性能的关键设计组件。我们证明，如色氨酸系统中所见，多重反馈回路基序能够在保持快速响应以实现稳态的同时，对系统参数的变化具有稳健的性能。优异的性能，如果源于设计原则，则是内在的，因此，对于任何类似设计的系统，无论是自然的还是工程的，都是固有的。在双罐系统上的多反馈回路设计的实验工程实现支持了该设计提供的鲁棒性属性的通用性。
Biological networks have evolved through adaptation in uncertain environments. Of the different possible design paradigms, some may offer functional advantages over others. These designs can be quantified by the structure of the network resulting from molecular interactions and the parameter values. One may, therefore, like to identify the design motif present in the evolved network that makes it preferable over other alternatives. In this work, we focus on the regulatory networks characterized by serially arranged processes, which are regulated by multiple feedback loops. Specifically, we consider the tryptophan system present in Escherichia coli, which may be conceptualized as three processes in series, namely transcription, translation and tryptophan synthesis. The multiple feedback loop motif results from three distinct negative feedback loops, namely genetic repression, mRNA attenuation and enzyme inhibition. A framework is introduced to identify the key design components of this network responsible for its physiological performance. We demonstrate that the multiple feedback loop motif, as seen in the tryptophan system, enables robust performance to variations in system parameters while maintaining a rapid response to achieve homeostasis. Superior performance, if arising from a design principle, is intrinsic and, therefore, inherent to any similarly designed system, either natural or engineered. An experimental engineering implementation of the multiple feedback loop design on a two-tank system supports the generality of the robust attributes offered by the design.