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arXiv 0802.1223q-bio.CBq-bio.MN
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大肠杆菌乳糖操纵子诱导过程中双稳态的决定因素

Determinants of bistability in induction of the Escherichia coli lac operon

David W. Dreisigmeyer, Jelena Stajic, Ilya Nemenman, William S. Hlavacek, Michael E. Wall

摘要:

我们已经开发了一个数学模型的大肠杆菌乳糖操纵子的表达调控,并研究了在没有外部葡萄糖的情况下,其稳态诱导行为的双稳态。数值分析方程描述人工诱导剂调节揭示了两个自然的双稳态参数,可用于控制诱导剂浓度的范围内,该模型表现出双稳态。通过调整这些双稳态参数,我们发现了一系列生物药理学上合理的系统,其与实验确定的硫代甲基半乳糖苷诱导的β-区域一致(Ozbudak等人,Nature 427:737,2004)。该模型预测,双稳态可以被废除时,被动运输或通透出口变得足够大,前一种情况下是特别相关的诱导异丙基-β,D-硫代半乳糖苷。为了模拟乳糖的调节,我们开发了类似的方程,其中异乳糖是乳糖代谢中的代谢中间体,也是乳糖的天然诱导物。对于生物药理学合理的参数值,这些方程不产生双稳态响应乳糖诱导,但是,系统与非物理小渗透依赖性的出口效应可以表现出少量的双稳态参数值的有限范围。这些结果对乳糖操纵子在大肠杆菌自然环境中的双稳态的相关性提出了质疑。大肠杆菌,并有助于阐明现有的理论研究,解决这个问题之间的争议。这些结果也表明了一种实验方法来解决的相关性,乳糖操纵子中的双稳态在自然环境中的E。杆菌

英文摘要:

We have developed a mathematical model of regulation of expression of the Escherichia coli lac operon, and have investigated bistability in its steady-state induction behavior in the absence of external glucose. Numerical analysis of equations describing regulation by artificial inducers revealed two natural bistability parameters that can be used to control the range of inducer concentrations over which the model exhibits bistability. By tuning these bistability parameters, we found a family of biophysically reasonable systems that are consistent with an experimentally determined bistable region for induction by thio-methylgalactoside (Ozbudak et al. Nature 427:737, 2004). The model predicts that bistability can be abolished when passive transport or permease export becomes sufficiently large; the former case is especially relevant to induction by isopropyl-beta, D-thiogalactopyranoside. To model regulation by lactose, we developed similar equations in which allolactose, a metabolic intermediate in lactose metabolism and a natural inducer of lac, is the inducer. For biophysically reasonable parameter values, these equations yield no bistability in response to induction by lactose; however, systems with an unphysically small permease-dependent export effect can exhibit small amounts of bistability for limited ranges of parameter values. These results cast doubt on the relevance of bistability in the lac operon within the natural context of E. coli, and help shed light on the controversy among existing theoretical studies that address this issue. The results also suggest an experimental approach to address the relevance of bistability in the lac operon within the natural context of E. coli.

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