Figure 1.
(A) Schematic illustration of the optimal metabolic network identification approach. Changes in the model reaction set lead to changes in the FBA-predicted optimal flux distribution (yellow) that can be compared to the experimental fluxes (red).
(B) Bilevel optimization scheme for optimal metabolic network identification.
Table 1.
Potential Applications of the OMNI Method
Table 2.
Experimentally Measured Physiological Parameters of Unevolved and Evolved Knockout Strains and Predicted Growth Rates from E. coli iJR904 Model
Table 3.
Reaction Bottlenecks for the pgiE1, ppcE1, ppcE2, tpiE1, and tpiE2 Strains Identified Using the OMNI Approach
Figure 2.
The Dependence of the Model Prediction Errors on the Number of Reactions Deleted from the Parental Strain Model
(A) The overall combined intracellular and growth rate prediction error as measured by the percentage of the OMNI objective value for the optimal modified model compared with the objective value for the parental strain model.
(B) The growth rate prediction error (percentage of the experimental growth rate) for the optimal modified model identified by the OMNI method.
Figure 3.
Correspondence between Bottleneck Reactions Identified by the OMNI Approach and Gene Expression Changes in the Evolved Knockout Strains Relative to the Wild-Type E. coli Strain
Expression changes, reported as log2 ratios and statistically significant expression changes (see Materials and Methods for details) in each evolved strain, are shown by +/− signs depending on the direction of the change. The reaction names are listed in the first column and the corresponding genes are listed in the second column. The genes corresponding to the best combination of reaction bottlenecks of up to three reactions identified by the OMNI approach (Table 3) for each strain are shown by white boxes.
Table 4.
Physiological Parameters of the 60-d Evolved pfkA-pta Strains under Anaerobic Conditions
Table 5.
Reaction Bottlenecks Identified Using the OMNI Approach for the Evolved Lactate-Overproducing Strains pfkA-ptaE1–3
Table 6.
Descriptions of Variable Names Used in Equations 1–4