Adaptive evolution of E. coli mutants. (A-B) Adaptive evolution of lactate producing E. coli strains for 60 days. The data from the lactate producing strains  were compared to integrated metabolic and regulatory model predictions. The production capabilities for each mutant was calculated without considering transcriptional regulation (blue) and considering transcriptional regulation (green). Experimentally observed trajectories are shown for every 10 days of adaptive evolution on the model predicted solution spaces. (C) Model predictions for adaptively evolved E. coli strains grown on malate. Previously reported data on the adaptive evolution of single gene knockout strains  was compared to simulations of the gene deletion mutants using the metabolic model (blue) and the integrated metabolic and regulatory model (green). The relative growth rates (experimentally observed/model predicted) were calculated for each strain at the last day of evolution using the two models. Error bars indicate one experimental standard deviation among two or three independently evolved strains.