期刊
BIOCHEMICAL ENGINEERING JOURNAL
卷 110, 期 -, 页码 59-70出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bej.2016.01.013
关键词
Metabolic control analysis; Allosteric regulation; Metabolic networks; Kinetic models; Kinetic modeling; Prediction performance; Systems metabolic engineering
资金
- FCT, through IDMEC, under LAETA [UID/EMS/50022/2013]
- FCT [SFRH/BPD/80784/2011]
- Program Investigador FCT from FCT [IF/00653/2012]
- European Social Fund (ESF) through the Operational Program Human Potential (POPH)
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.
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