Adam M. Feist and Bernhard Ø. Palsson. Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093
The use of systems biology methods in metabolic engineering applications is on the rise. Aiding these efforts are computational models that allow for the analysis of cellular processes on the genomic-scale and the integration of high-throughput data sets. Genome-scale metabolic models specifically are important in metabolic engineering applications due their ability to predict the effects of specific genetic manipulations on substrate uptake, desired byproduct secretion, and growth rate. Here, we present, i.) a genome-scale metabolic reconstruction of E. coli as an analysis platform for metabolic engineering, ii.) the modeling and adaptation methods applied to engineer production strains of E. coli, and iii.) current experimental validation for the demonstration of strain performance. The genome-scale reconstruction of E. coli, iAF1260, is the largest and most complete reconstruction of a micro-organism to date. Coupled with our modeling approaches, we present the use of adaptive evolution as a design principle in strain construction.
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systemsbiology.ucsd.edu/
