Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus

dc.contributor.authorFigueiredo, Ana Sofiaen_ZA
dc.contributor.authorKouril, Theresaen_ZA
dc.contributor.authorEsser, Dominiken_ZA
dc.contributor.authorHaferkamp, Patricken_ZA
dc.contributor.authorWieloch, Patriciaen_ZA
dc.contributor.authorSchomburg, Dietmaren_ZA
dc.contributor.authorRuoff, Peteren_ZA
dc.contributor.authorSiebers, Bettinaen_ZA
dc.contributor.authorSchaber, Jorgen_ZA
dc.date.accessioned2018-11-14T11:54:11Z
dc.date.available2018-11-14T11:54:11Z
dc.date.issued2017-07-10
dc.descriptionCITATION: Figueiredo, A. S., et al. 2017. Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus. PLoS ONE 12(7):e0180331, doi:10.1371/journal.pone.0180331.en_ZA
dc.descriptionThe original publication is available at https://journals.plos.org/plosoneen_ZA
dc.description.abstractSulfolobus 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.en_ZA
dc.description.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180331
dc.description.versionPublisher's versionen_ZA
dc.format.extent25 pages : illustrationsen_ZA
dc.identifier.citationFigueiredo, A. S., et al. 2017. Systems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricus. PLoS ONE 12(7):e0180331, doi:10.1371/journal.pone.0180331en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0180331
dc.identifier.urihttp://hdl.handle.net/10019.1/104689
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectSulfolobus solfataricusen_ZA
dc.subjectEntner-Doudoroff (ED) pathwayen_ZA
dc.subjectEntner-Doudoroff (ED) pathway -- Mathematical modelen_ZA
dc.subjectSystems biologyen_ZA
dc.titleSystems biology of the modified branched Entner-Doudoroff pathway in Sulfolobus solfataricusen_ZA
dc.typeArticleen_ZA
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