Design of Optimally Constructed Metabolic Networks of Minimal Functionality

David E Ruckerbauer, Christian Jungreuthmayer and Jürgen Zanghellini

PLOS ONE, 2014, vol. 9, issue 3, 1-10

Abstract: Background: Metabolic engineering aims to design microorganisms that will generate a product of interest at high yield. Thus, a variety of in silico modeling strategies has been applied successfully, including the concepts of elementary flux modes (EFMs) and constrained minimal cut sets (cMCSs). The EFMs (minimal, steady state pathways through the system) can be calculated given a metabolic model. cMCSs are sets of reaction deletions in such a network that will allow desired pathways to survive and disable undesired ones (e.g., those with low product secretion or low growth rates). Grouping the modes into desired and undesired categories had to be done manually until now. Results: Although the optimal solution for a given set of pathways will always be found with the currently available tools, manual selection may lead to a sub-optimal solution with respect to a metabolic engineering target. A small change in the selection of modes can reduce the number of necessary deletions while only slightly reducing production. Based on our recently introduced formulation of cut set calculations using binary linear programming, we suggest an algorithm that does not require manual selection of the desired pathways. Conclusions: We demonstrated the principle of our algorithm with the help of a small toy network and applied it to a model of E. coli using different design objectives. Furthermore we validated our method by reproducing previously obtained results without requiring manual grouping of modes.

Date: 2014
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092583 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 92583&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0092583

DOI: 10.1371/journal.pone.0092583

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().