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With abundant genomic data now available, methods must be formulated to utilize this pool of data to yield meaningful biological information. Using a constraints-based approach, a genome-scale whole cell model has been constructed for Escherichia coli that can be used to predict behavioral characteristics of the K-12 MG1655 wild-type strain. In particular, phenotype phase-plane analysis can be used to distinguish different operating states of E. coli with particular interest in defining a line of optimal growth. A hypothesis was formulated that E. coli will naturally optimize its growth and exhibit a phenotype corresponding to the predicted line of optimality. Evolution experiments were carried out for 500 to 1000 generations where E. coli were allowed to naturally accumulate mutations. Various carbon sources with different entry points into central metabolism were used to test the robustness of the model. The experimental results showed that over the course of evolution, E. coli evolved towards the line of optimality and remained along the line of optimality while increasing its substrate uptake rate, oxygen uptake rate, and specific growth rate. Thus, the constraints-based model of E. coli serves as an accurate predictive tool in determining the growth behavior of E. coli under the parameters tested.
Engineering in Medicine and Biology, 2002. 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society EMBS/BMES Conference, 2002. Proceedings of the Second Joint (Volume:3 )
Date of Conference: 23-26 Oct. 2002