Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus.
Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus.
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DOI：
10.1371/journal.pone.0180331
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Schaber J
中科院分区：
文献类型：
--
作者：
Figueiredo AS;Kouril T;Esser D;Haferkamp P;Wieloch P;Schomburg D;Ruoff P;Siebers B;Schaber J
硫磺硫化叶菌（Sulfolobus solfataricus）是一种嗜热嗜酸菌，在陆地温泉（solfatares）中生长，最佳生长温度为80°C，pH值为2-4。它通过改良的Entner-Doudoroff（艾德）途径将特定碳源（如D-葡萄糖）分解代谢为丙酮酸。该途径有两个平行的分支，半磷酸化和非磷酸化。然而，S.solfataricus在这种极端环境中的鲁棒性和适应性的策略尚未完全理解。在这里，我们提出了第一个动态数学模型的艾德途径参数化定量实验数据。这些数据由分支途径在70°C和80°C下的酶活性以及野生型和半磷酸化分支的代谢工程敲除在相同温度下的代谢组学数据组成。我们使用验证模型来解决两个问题：1。这个系统在其最佳生长温度下对扰动是否更鲁棒？2.艾德对删除和扰动是否稳健？我们采用了系统生物学的方法来回答这些问题，并获得进一步的知识，这个生物系统的涌现特性。具体来说，我们分别应用确定性方法和随机方法来研究系统的灵敏度和鲁棒性。我们在这里提出的数学模型，表明：1。艾德途径的稳态代谢物浓度在80°C下比在70°C下对随机内部扰动始终更稳健; 2.当面临任一分支的敲除时，这些代谢物浓度非常稳健。与此观察相关联，这两个分支在代谢产物产生和通量控制水平上显示出不同的特性。这些新的结果揭示了酶动力学和代谢组学如何与数学建模协同作用，以揭示S.solfataricus中艾德途径在其适应性和鲁棒性方面的新的系统特性。
Sulfolobus solfataricus is a thermoacidophilic Archaeon that thrives in terrestrial hot springs (solfatares) with optimal growth at 80°C and pH 2–4. It catabolizes specific carbon sources, such as D-glucose, to pyruvate via the modified Entner-Doudoroff (ED) pathway. This pathway has two parallel branches, the semi-phosphorylative and the non-phosphorylative. However, the strategy of S.solfataricus to endure in such an extreme environment in terms of robustness and adaptation is not yet completely understood. Here, we present the first dynamic mathematical model of the ED pathway parameterized with quantitative experimental data. These data consist of enzyme activities of the branched pathway at 70°C and 80°C and of metabolomics data at the same temperatures for the wild type and for a metabolic engineered knockout of the semi-phosphorylative branch. We use the validated model to address two questions: 1. Is this system more robust to perturbations at its optimal growth temperature? 2. Is the ED robust to deletion and perturbations? We employed a systems biology approach to answer these questions and to gain further knowledge on the emergent properties of this biological system. Specifically, we applied deterministic and stochastic approaches to study the sensitivity and robustness of the system, respectively. The mathematical model we present here, shows that: 1. Steady state metabolite concentrations of the ED pathway are consistently more robust to stochastic internal perturbations at 80°C than at 70°C; 2. These metabolite concentrations are highly robust when faced with the knockout of either branch. Connected with this observation, these two branches show different properties at the level of metabolite production and flux control. These new results reveal how enzyme kinetics and metabolomics synergizes with mathematical modelling to unveil new systemic properties of the ED pathway in S.solfataricus in terms of its adaptation and robustness.
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影响因子：
4.1
作者：
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