Fig 1.
Conceptual model of the Entner-Doudoroff (ED) pathway in S.solfataricus.
This pathway catabolizes D-glucose (Glc) to pyruvate (Pyr) and has two distinct branches: the semi-phosphorylative (spED) in blue and the non-phosphorylative (npED) in green. Both branches incorporate regulatory mechanisms (red lines). Black lines represent the common branches of the network and gray lines represent ADP/ATP phosphorylation/dephosphorylation and NADP/NADPH redox-reactions.
Fig 2.
Metabolome ratios for Glc, D-Gat, KDG, GA and Gly.
Metabolome ratios calculated with Eq 2. Comparison between the metabolomics experiments (metabolites Glc, D-Gat, KDG and Gly) and simulated metabolite concentrations. Relative difference between simulated and experimental levels in blue; simulated calculations in red; experimental values in orange.
Fig 3.
Comparison between and SS70°C for metabolite and flux steady states. A-B) Pie Chart. Inner circle: percentual contribution of each metabolite (A) or flux (B) steady states to the overall steady state at 70°C (SS70°C); Outer circle: percentual contribution of each metabolite (A) or flux (B) steady states to the overall steady state at 70°C (
) (0% contributions ignored); C-D) Bar Chart comparing the metabolite and flux steady states for
(Orange Bars), SS70°C (dark red bars) and the relative ratio between
and SS70°C (blue bars). The left y-axis refers to the
and SS70°C and the right y-axis (blue) refers to the relative ratio rc. C) Metabolite; D) Flux.
Table 1.
Metabolome ratios for Glc, D-Gat, KDG, GA and Gly for the WT and knockout.
Measured and simulated metabolite ratios of the ED pathway between PBL 2025ΔSSO3195 (spED = 0) and WT at 80°C.
Fig 4.
Matrix plot of the maximal sensitivities of the modified ED pathway in S. solfataricus at A) 70°C and B) 80°C. Columns represent the Metabolites and rows represent the Vmax. “+”and “-”indicate whether the maximal sensitivity was obtained for +20% or -20% variation, respectively.
Fig 5.
Stochastic external perturbations.
Histograms of Glc, (A), and Pyr (B), and the relative standard deviations (C) of these three metabolites, at 70°C and 80°C, when changes 50% around its original value. Red bars represent the model at 70°C and green ones at 80°C.
Fig 6.
Stochastic internal perturbations.
Histograms accounting for metabolites’ relative steady state variations after stochastically varying Vmax. Red: 70°C, Green: 80°C. A) Glc; B) Pyr; C) Gly; D) GA; E) RSD and network elements. # means counts.
Fig 7.
Robustness to uncertainty and branch deletion.
Histogram accounting for uncertainty and branch deletion at the level of Pyr steady state. Blue bars represent the histogram of Pyr production when the npED branch is set to zero (NP = 0), green bars represent the histogram of Pyr production when the spED branch is set to zero (SP = 0), and red bars represent the histogram of Pyr production for the wild type (WT). A) Relative steady state values. B) Absolute steady state values. # represents counts.
Fig 8.
Perturbation of the negative feedforward reaction of the npED branch.
Stochastic perturbations on the feedforward parameters affecting VGK. A) Pathway diagram of the npED branch with perturbation on the feedforward connection; B) Parametric plot relating Pyr and Gly with feedforward perturbations (red) and without feedforward perturbations (blue); C) Histogram of Pyr steady states with feedforward perturbations (red) and without feedforward perturbations (blue); D) Histogram of Gly steady states with feedforward perturbations (red) and without feedforward perturbations (blue).