Escherichia coli is one of the most explored microorganisms. It is caused by several facts. The first one is a sufficiently easy growth of this bacterium on all basic carbon sources (both at aerobic and anaerobic conditions). The second one is that E. coli genome is sequenced completely. Furthermore, it is considered that metabolic functions are observed for more then 80% of genes. The third one is that E. coli cells are very often used in bioengineering studies and biotechnological production. No wonder that such attention to this bacteria allows to use E. coli as a model microorganism for studying of the metabolism functioning and regulation. This is a prominent role because this problem is one of the most important in modern biochemistry. For more then 50 years studying of this problem the impressive content of experimental data characterizing metabolic systems from various sides has been collected. Moreover, in the 21st century development of such experimental techniques as metabolomics, proteomics, transcriptomics etc. allows quantitative describing metabolic systems behavior. However, one of the main reasons which suppresses studying of metabolism functioning and regulation by the present time is an inadequate progress of theoretical approaches for analysis and processing of various experimental data. Exactly this task should be resolved using methods of kinetic modeling of biochemical pathways as the more powerful method of metabolic modeling. Kinetic modeling allows mathematical describing and analysis of  practically all types of biochemical quantitative data, taking into model account all information about structure, stoichiometry and regulation realizing in the system. On the over hand kinetic modeling allows making predictions, characterizing systems biochemical properties as well. Development of such model for metabolic pathways of E. coli, which contains from one side maximum of experimental information and from the other side could be used for a design of further studies and making predictions is a one of the today prominent systems biology tasks.

In the Institute for Systems Biology SPb we have been developing kinetic models of E. coli metabolism for the last several years. Thus, we had made the first steps in this field in the 2000-2002 years, when the initial kinetic models of glycolysis, TCA cycle and biosynthesis of basic biochemical building blocks (such as amino acids, purine and pyrimidine nucleotides) had been developed. Further elaboration allowed us to increase our activity in the understanding of E. coli metabolism functioning and expanded a range of metabolic pathways  which were taken into model account. By the present time we have developed kinetic models of more then 30 E. coli biochemical pathways and regulatory systems:

• PTS (PEP-dependent transferase system)
• Glycolysis
• Gluconeogenesis
• Pentose monophosphate pathway
• Entner-Doudoroff pathway
• Anaerobic (branched) Krebs cycle
• Aerobic Krebs cycle
• Glyoxylate bypass
• Respiratory chain and oxidative phosphorylation
• Pathways of ammonia assimilation
• Anaerobic dissimilation of pyruvate
• Metabolism of fatty acids
• Pathways of amino acids biosynthesis
• de novo Pathway of pyrimidines biosynthesis
• de novo Pathway of purine biosynthesis
• Pyrimidines’ salvage pathways
• Purines’ salvage pathways
• Lac operon gene expression

In the framework of these models we have developed more than 300 detail mathematical descriptions of individual enzymes (from one thousand enzymes observed for E. coli cells) and 10 gene expression regulatory systems. Moreover, modeling of E. coli pathways serves as a training ground for the development and testing of the modeling approach, which is used in our Institute for complex investigations for systems pharmacology and biotechnology. For example, based on the E. coli objects we have developed strategies for the kinetic models development of allosteric enzymes, multi enzyme complexes and gene expression regulatory systems. Part of the models has been applied for the biotechnological experiments such as strain improvement (e.g. kinetic model of pyrimidine biosynthesis).

In these pages of the website we represent several materials related to the E. coli metabolism modeling. Of course, it is a brief and incomplete description. However, we tried to stress an attention on the most obvious and interesting results of this large-scale modeling project. All these results are urged to accentuate the importance of systems biology modeling approaches for the investigation of the metabolism functioning and regulation.