Applied Biochemistry and Microbiology

, Volume 46, Issue 7, pp 671–687 | Cite as

Metabolic engineering in silico

  • V. A. LikhoshvaiEmail author
  • T. M. Khlebodarova
  • M. T. Ree
  • N. A. Kolchanov


This review briefs on the main directions in the field of mathematical modeling of metabolic processes aimed at a rational design of genetically modified organisms. The class of generalized Hill functions is described, and their application to modeling of nonlinear processes in Escherichia coli metabolic systems is illustrated by several examples. A model for the pyrimidine biosynthesis in E. coli, taking into account the nonlinear effects of a negative allosteric regulation of enzyme activities involved in the control of the subsequent stages by the end products of synthesis, is considered. It has been shown that the model displays its own continuous oscillation mode of functioning with a period of approximately 50 min, which is close to the duration of E. coli cell cycle. The need in considering the nonlinear effects in the models as essential elements in the function of metabolic systems far from equilibrium is discussed.

Key words

mathematical modeling metabolic engineering generalized Hill functions regulation Escherichia coli 



model of target objects


generalized Hill function




adenine phosphoribosyltransferase


aspartate transcarbamoylase


carbamoyl aspartate


carbamoyl phosphate


carbamoyl phosphate synthetase


cytosine triphosphate synthetase


tryptophansensitive 3-deoxy-D-arabinoheptulonate-7-phosphate synthetase




dihydroorotate dehydrogenase








NAD(P)-dependent lactate dehydrogenase 2


nucleoside diphosphate kinase


orotidine monophosphate


orotidine monophosphate decarboxylase


orotate phosphoribosyl transferase








pyruvate formate lyase




ribonucleoside diphosphate reductase


ribonucleoside triphosphate reductase



UMP kinase

uridine monophosphate kinase


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Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  • V. A. Likhoshvai
    • 1
    • 2
    Email author
  • T. M. Khlebodarova
    • 1
  • M. T. Ree
    • 1
  • N. A. Kolchanov
    • 1
    • 2
  1. 1.Institute of Cytology and Genetics, Siberian BranchRussian Academy of SciencesNovosibirskRussia
  2. 2.Novosibirsk State UniversityNovosibirskRussia

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