论文标题

大肠杆菌中色氨酸的运输,合成和代谢的布尔模型

Boolean models of the transport, synthesis, and metabolism of tryptophan in Escherichia Coli

论文作者

Deal, Isadora, Macauley, Matthew, Davies, Robin

论文摘要

大肠杆菌中的色氨酸(TRP)操纵子代表负责从绒毛酸中合成氨基酸色氨酸的蛋白质,自1960年代发现以来,它一直是研究最精心研究的基因网络之一。色氨酸酶(TNA)操纵子为运输和代谢所需的蛋白质编码。这两者都是在大量动力学假设下用延迟微分方程单独建模的。最近的工作为TNA操纵子的可行行为提供了有力的证据。 (Orozco,2019年)的作者确定了一个中等范围的色氨酸,其中系统具有两个稳定的稳态,并且它们通过实验重现了这些稳定的稳态。在本文中,我们将展示布尔模型如何捕获这种双重性。我们还将开发和分析TRP操纵子的布尔模型。最后,我们将结合这两个,以创建色氨酸传输,合成和代谢的单一布尔模型。在这个合并模型中,双重性消失了,大概反映了TRP操纵子产生色氨酸并驱动系统朝向体内平衡的能力。所有这些模型都具有更长的吸引子,我们称之为“同步工件”,它消失在异步自动机中。奇怪的是,这与大肠杆菌中阿拉伯糖操纵子的最新布尔模型的行为相匹配,我们讨论了一些沿这些线路出现的开放性问题。

The tryptophan (trp) operon in E. coli codes for the proteins responsible for the synthesis of the amino acid tryptophan from chorismic acid, and has been one of the most well-studied gene networks since its discovery in the 1960s. The tryptophanase (tna) operon codes for proteins needed to transport and metabolize it. Both of these have been modeled individually with delay differential equations under the assumption of mass-action kinetics. Recent work has provided strong evidence for bistable behavior of the tna operon. The authors of (Orozco, 2019) identified a medium range of tryptophan in which the system has two stable steady-states, and they reproduced these experimentally. In this paper, we will show how a Boolean model can capture this bistability. We will also develop and analyze a Boolean model of the trp operon. Finally, we will combine these two to create a single Boolean model of the transport, synthesis, and metabolism of tryptophan. In this amalgamated model, the bistability disappears, presumably reflecting the ability of the trp operon to produce tryptophan and drive the system toward homeostasis. All of these models have longer attractors that we call "artifacts of synchrony", which disappear in the asynchronous automata. This curiously matches the behavior of a recent Boolean model of the arabinose operon in E. coli, and we discuss some open-ended questions that arise along these lines.

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