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Designing metabolic engineering strategies with genome-scale metabolic flux modeling

Authors Yen JY, Tanniche I, Fisher AK, Gillaspy GE, Bevan DR, Senger RS

Received 2 September 2014

Accepted for publication 18 November 2014

Published 30 January 2015 Volume 2015:5 Pages 93—105

DOI https://doi.org/10.2147/AGG.S58494

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr John Martignetti

Jiun Y Yen,1,2 Imen Tanniche,1 Amanda K Fisher,1–3 Glenda E Gillaspy,2 David R Bevan,2,3 Ryan S Senger1

1Department of Biological Systems Engineering, 2Department of Biochemistry, 3Genomics, Bioinformatics, and Computational Biology Interdisciplinary Program, Virginia Tech, Blacksburg, VA, USA


Abstract: New in silico tools that make use of genome-scale metabolic flux modeling are improving the design of metabolic engineering strategies. This review highlights the latest developments in this area, explains the interface between these in silico tools and the experimental implementation tools of metabolic engineers, and provides a way forward so that in silico predictions can better mimic reality and more experimental methods can be considered in simulation studies. The several methodologies for solving genome-scale models (eg, flux balance analysis [FBA], parsimonious FBA, flux variability analysis, and minimization of metabolic adjustment) all have unique advantages and applications. There are two basic approaches to designing metabolic engineering strategies in silico, and both have demonstrated success in the literature. The first involves: 1) making a genetic manipulation in a model; 2) testing for improved performance through simulation; and 3) iterating the process. The second approach has been used in more recently designed in silico tools and involves: 1) comparing metabolic flux profiles of a wild-type and ideally engineered state and 2) designing engineering strategies based on the differences in these flux profiles. Improvements in genome-scale modeling are anticipated in areas such as the inclusion of all relevant cellular machinery, the ability to understand and anticipate the results of combinatorial enrichment experiments, and constructing dynamic and flexible biomass equations that can respond to environmental and genetic manipulations.

Keywords: genome-scale modeling, genome-scale modeling, flux balance analysis, flux variability analysis, minimization of metabolic adjustment, metabolic bottleneck, pathway optimization

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