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The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli

Abstract

The number and scope of methods developed to interrogate and use metabolic network reconstructions has significantly expanded over the past 15 years. In particular, Escherichia coli metabolic network reconstruction has reached the genome scale and been utilized to address a broad spectrum of basic and practical applications in five main categories: metabolic engineering, model-directed discovery, interpretations of phenotypic screens, analysis of network properties and studies of evolutionary processes. Spurred on by these accomplishments, the field is expected to move forward and further broaden the scope and content of network reconstructions, develop new and novel in silico analysis tools, and expand in adaptation to uses of proximal and distal causation in biology. Taken together, these efforts will solidify a mechanistic genotype-phenotype relationship for microbial metabolism.

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Figure 1: Formulation and use of GEMs as a four-step process.
Figure 2: The iterative reconstruction and history of the E. coli metabolic network.
Figure 3: Applications of the genome-scale model (GEM) of E. coli divided into five categories.
Figure 4: Summary of the in silico methods used in the 64 published E. coli GEM studies reviewed here.
Figure 5: Comparison of computation and experimental data: identification of agreements and disagreements.

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Acknowledgements

We would like to thank Andrew Joyce, Jennifer Reed, Daniel Segre, Nathan Price, Markus Herrgard and Christian Barrett for their invaluable insight. A.M.F. is supported by National Institutes of Health R01 GM057089 grant.

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Correspondence to Bernhard Ø Palsson.

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Feist, A., Palsson, B. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat Biotechnol 26, 659–667 (2008). https://doi.org/10.1038/nbt1401

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