Computing the shortest elementary flux modes in genome-scale metabolic networks.
BACKGROUND
Elementary flux modes (EFMs) represent a key concept to analyze metabolic networks from a pathway-oriented perspective. In spite of considerable work in this field, the computation of the full set of elementary flux modes in large-scale metabolic networks still constitutes a challenging issue due to its underlying combinatorial complexity.


RESULTS
In this article, we illustrate that the full set of EFMs can be enumerated in increasing order of number of reactions via integer linear programming. In this light, we present a novel procedure to efficiently determine the K-shortest EFMs in large-scale metabolic networks. Our method was applied to find the K-shortest EFMs that produce lysine in the genome-scale metabolic networks of Escherichia coli and Corynebacterium glutamicum. A detailed analysis of the biological significance of the K-shortest EFMs was conducted, finding that glucose catabolism, ammonium assimilation, lysine anabolism and cofactor balancing were correctly predicted. The work presented here represents an important step forward in the analysis and computation of EFMs for large-scale metabolic networks, where traditional methods fail for networks of even moderate size.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Friedrich-Schiller-University Jena, 07743 Jena, Germany.
Luis F
LF
de Figueiredo
Adam
A
Podhorski
Angel
A
Rubio
Christoph
C
Kaleta
John E
JE
Beasley
Stefan
S
Schuster
Francisco J
FJ
Planes
D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D048230:Corynebacterium glutamicum / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D016680:Genome, Bacterial; D053858:Metabolic Networks and Pathways / Q000235:genetics