Development of an accurate kinetic model for the central carbon metabolism of Escherichia coli

Microbial Cell Factories

Research

Yurie Sugimoto¹  Yu Matsuoka¹  Nusrat Jahan¹  Hiroyuki Kurata²  Kazuhiro Maeda³ 

[1] Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, 820-8502, Fukuoka, Japan;Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, 820-8502, Fukuoka, Japan;Biomedical Informatics R&D Center, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, 820-8502, Fukuoka, Japan;Frontier Research Academy for Young Researchers, Kyushu Institute of Technology, 1-1 Sensui-cho, Tobata, 804-8550, Kitakyushu, Fukuoka, Japan;Biomedical Informatics R&D Center, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, 820-8502, Fukuoka, Japan;

关键词: Systems biology;    Rational design;    Dynamic model;    Enzyme kinetics;    Transcription factor;    Signal transduction;    Allosteric enzyme;   

DOI  :  10.1186/s12934-016-0511-x

 received in 2016-05-02, accepted in 2016-06-08,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA kinetic model provides insights into the dynamic response of biological systems and predicts how their complex metabolic and gene regulatory networks generate particular functions. Of many biological systems, Escherichia coli metabolic pathways have been modeled extensively at the enzymatic and genetic levels, but existing models cannot accurately reproduce experimental behaviors in a batch culture, due to the inadequate estimation of a specific cell growth rate and a large number of unmeasured parameters.ResultsIn this study, we developed a detailed kinetic model for the central carbon metabolism of E. coli in a batch culture, which includes the glycolytic pathway, tricarboxylic acid cycle, pentose phosphate pathway, Entner-Doudoroff pathway, anaplerotic pathway, glyoxylate shunt, oxidative phosphorylation, phosphotransferase system (Pts), non-Pts and metabolic gene regulations by four protein transcription factors: cAMP receptor, catabolite repressor/activator, pyruvate dehydrogenase complex repressor and isocitrate lyase regulator. The kinetic parameters were estimated by a constrained optimization method on a supercomputer. The model estimated a specific growth rate based on reaction kinetics and accurately reproduced the dynamics of wild-type E. coli and multiple genetic mutants in a batch culture.ConclusionsThis model overcame the intrinsic limitations of existing kinetic models in a batch culture, predicted the effects of multilayer regulations (allosteric effectors and gene expression) on central carbon metabolism and proposed rationally designed fast-growing cells based on understandings of molecular processes.

【 授权许可】

CC BY   
© The Author(s) 2016

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