title: Development of an accurate kinetic model for the central carbon metabolism of Escherichia coli.
abstract: BACKGROUND
  A 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka, 820-8502, Japan.
authors.forename: Nusrat
authors.initials: N
authors.lastname: Jahan
authors.affiliation: Frontier Research Academy for Young Researchers, Kyushu Institute of Technology, 1-1 Sensui-cho, Tobata, Kitakyushu, Fukuoka, 804-8550, Japan.|Biomedical Informatics R&D Center, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka, 820-8502, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka, 820-8502, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Matsuoka
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka, 820-8502, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka, 820-8502, Japan. kurata@bio.kyutech.ac.jp.|Biomedical Informatics R&D Center, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka, 820-8502, Japan. kurata@bio.kyutech.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurata
mesh_terms: D002244:Carbon / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D008954:Models, Biological
chemical_list: D029968:Escherichia coli Proteins; D002244:Carbon
keywords: Allosteric enzyme; Dynamic model; Enzyme kinetics; Rational design; Signal transduction; Systems biology; Transcription factor