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(Step 2): A linear transformation from the expression of the phenotype-associated genes, to reactions' upper bound (maximal flux capacity) is applied ('Materials and methods').
This is achieved by setting maximal flux capacity constraints on a selected subset of reactions in the generic species model, according to their associated gene expression levels and phenotypic data.
Underlying reasons at the molecular level are not known but our results indicated that the maximal flux capacity of UG is allosterically controlled in xylose-utilizing recombinant S. cerevisiae.
Results from MCA and the predictability study led to the suggestion that in contrast to network modifications executed downstream from the XA pathway, overexpression of XR or XDH positively affected the maximal flux capacity of UG.
Results from strain-to-strain metabolic control analysis indicated that activity levels of XR and the maximal flux capacity of the upper glycolysis (UG; both ≥ tenfold higher in CBS4435) contributed predominantly to phenotype differentiation while reactions from the oxidative pentose phosphate pathway played minor roles.
It then proceeds as follows: (1) A set of genes that are significantly correlated with the key phenotype of interest is determined (Supplementary file 2A); (2) The maximal flux capacity of reactions associated with the genes identified in (1) is modified according to the directionality and level of their corresponding gene expression level.
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Distribution of maximum flux capacities for all model metabolites.
The difference between these maximum production and consumption fluxes is a value that we term the maximum flux capacity (MFC).
These responses indicate a blunting of oxidative phosphorylation linked to ATP synthase and a decreased maximal electron flux capacity in the uncoupled state induced by addition of FCCP, respectively.
We use the maximal flux value as the corresponding reaction flux capacity.
For each reaction in the network, the reaction flux capacity is the set to the maximal flux value of the reaction from the flux distributions.
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