Identification of flux control in metabolic networks using non-equilibrium thermodynamics
Journal article, 2010

A method is presented to identify flux controlling reactions in metabolic networks using experimentally determined flux distributions. The method is based on the application of Ziegler's principle for the maximization of entropy production. According to this principle a metabolic network tends to maximize the entropy production rate while satisfying mass balances and maximal rate constraints. Experimental flux data corresponding to four different metabolic states of Saccharomyces cerevisiae were used to identify the corresponding flux controlling reactions. The bottleneck nature of several of the identified reactions was confirmed by earlier studies on over-expression of the identified target genes. The method also explains the failure of all the previous trials of increasing the glycolysis rate by direct over-expression of several glycolytic enzymes. These findings point to a wider use of the method for identification of novel targets for metabolic engineering of microorganisms used for sustainable production of fuels and chemicals.

Author

Sergio Bordel

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences, System Biology

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 12 4 369-377

Areas of Advance

Information and Communication Technology

Life Science Engineering (2010-2018)

Subject Categories

Bioinformatics and Systems Biology

Other Industrial Biotechnology

DOI

10.1016/j.ymben.2010.03.001

More information

Latest update

7/22/2019