4.6 Article

Control analysis of the impact of allosteric regulation mechanism in a Escherichia coli kinetic model: Application to serine production

Journal

BIOCHEMICAL ENGINEERING JOURNAL
Volume 110, Issue -, Pages 59-70

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bej.2016.01.013

Keywords

Metabolic control analysis; Allosteric regulation; Metabolic networks; Kinetic models; Kinetic modeling; Prediction performance; Systems metabolic engineering

Funding

  1. FCT, through IDMEC, under LAETA [UID/EMS/50022/2013]
  2. FCT [SFRH/BPD/80784/2011]
  3. Program Investigador FCT from FCT [IF/00653/2012]
  4. European Social Fund (ESF) through the Operational Program Human Potential (POPH)

Ask authors/readers for more resources

Kinetic modeling is a key aspect of systems biology with biotechnological applications. However, a limitation of building kinetic models of metabolism (particularly from stoichiometric reconstructions of metabolic networks) is that they often ignore the allosteric regulators. This can cause discrepancies in the model predictions. In this paper, we derived an approximated lin-log ODE model of the Escherichia coli central carbon metabolism, with and without metabolite-enzyme regulators. Next, we analyzed the influence of incorporating this level of metabolite-enzyme interactions in the metabolic network by performing several in silico single-gene knockouts and enzyme under-/over-expression changes. Through comparing these model predictions with those generated with a reference mechanistic kinetic model for E. coli, it is shown that including of allosteric regulation affects the flux control patterns over serine production and reveals more details of the model behavior in a general sense. The present work demonstrates that the regulatory (allosteric) structure in metabolic networks plays an essential role to further improve kinetic model prediction capabilities. The incorporation of allosteric regulation interactions in building a kinetic model can lead to different hypotheses in order to suggest enzyme targets for strain design through metabolic engineering. (C) 2016 Elsevier B.V. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available