Abstract
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.
Highlights
Sulfolobus solfataricus (S. solfataricus) belongs to the Archaea, the third domain of life
Our conceptual model of the ED pathway of S. solfataricus (Fig 1) combines several published results on partial aspects of the central carbohydrate metabolism (CCM), such as a regulation motif accounting for phosphoglycerate kinase (VPGK) inhibition [20] and a feedforward accounting for glycerate kinase (VGK) inhibition
S. solfataricus is used as a model organism for resisting and surviving in extreme conditions, such as in simulated space environment [40]
Summary
Sulfolobus solfataricus (S. solfataricus) belongs to the Archaea, the third domain of life. D-glucose (Glc) conversion to Pyr in S. solfataricus does not proceed via the typical Embden-Meyerhof-Parnas (EMP) pathway (i.e. glycolysis), but through a modified version of the Entner-Doudoroff (ED) pathway [3] found in some aerobic bacteria [4,5,6,7,8,9] and fungi [10]. This modified ED pathway uses novel biocatalysts and has two branches —the non-phosphorylative (npED) and semi-phosphorylative (spED) [11,12,13]
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