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博士論文 / Development of a detailed kinetic model for the central carbon metabolism of Escherichia coli 大腸菌中央代謝の詳細な動力学的モデルの開発

著者

書誌事項

タイトル

Development of a detailed kinetic model for the central carbon metabolism of Escherichia coli

タイトル別名

大腸菌中央代謝の詳細な動力学的モデルの開発

著者名

Jahan Nusrat

学位授与大学

九州工業大学 (大学ID:0071) (CAT機関ID:KI000844)

取得学位

博士(情報工学)

学位授与番号

甲情工第318号

学位授与年月日

2017-03-24

注記・抄録

Background: Mathematical models are widely used and precious tools for the researcher to reconstruct and predict complex cellular system for our understanding of the living cells. A common type of mathematical model is the differential equation model, which particularly suitable to investigate the dynamic behavior of the metabolic networks and molecular interactions. The dynamic models provide significant insights on the dynamic response of microorganisms and predict those complex metabolic and gene regulatory networks generate particular biological behaviors. Both sciences (for example, biochemistry) and engineering (for example, metabolic engineering) angle, it is deeply essential to recognize the whole metabolic regulation mechanism of bacterial cells, like as Escherichia coli (E.coli). Out of many biological systems, E. coli central carbon metabolism has extensively been modeled. It has been studied at the enzymatic and genetic levels for the central metabolism in E. coli, however, the whole regulatory mechanism of this network remains to be analyzed. The specific gene knockout effect is important for the understanding of the role of metabolic pathway genes in metabolism. For practical applications, the main attention is the predictability of the model for specific gene knockouts. Results: In this thesis, we developed a detailed kinetic model for the central carbon metabolism of E. coli in both batch and continuous cultures to overcome intrinsic problems of the existing kinetic models, which includes the glycolysis pathway, tricarboxylic acid (TCA) cycle, pentose phosphate (PP) pathway, entner-doudoroff (ED) pathway, anaplerotic pathway, glyoxylate shunt, oxidative phosphorylation, phosphotransferase system (PTS), non-PTS as well as four transcriptional factors (TFs)- cAMP receptor protein (Crp), catabolite repressor/activator (Cra) protein, pyruvate dehydrogenase complex repressor (PdhR) protein and acetate operon repressor (IclR) protein. The kinetic parameters were estimated by a constrained optimization method on a supercomputer. The model accurately reproduced the dynamics of wild type (WT) and two genetic mutants (Δpgi, ΔpykF) in a batch culture, while estimating a specific growth rate based on reaction kinetics. In continuous culture, the proposed model more fitted with high dilution rate experimental data. Conclusion: We have developed a detailed kinetic model for the central carbon metabolism of E. coli which reproduced WT, Δpgi, ΔpykF without changing any parameter value. In the case of Δppc, our model can not reproduce exact experimental data, but, it reproduces the delay cell growth. The proposed model overcame the intrinsic limitations of the existing kinetic models in a batch culture. The simulation results were rather consistent with experimental data at a high dilution rate in continuous culture. The kinetic model predicts the effects of multiple layer regulations - gene regulation by TFs, and allosteric regulation, on the central carbon metabolisms. Concisely, we proposed a detailed kinetic model for the central carbon metabolism of E. coli which verified and validated by using many experimental data. The model can reproduce the experimental dynamic behaviors, while a small fraction of intracellular metabolite concentrations and fluxes were not adequately ensured by the experimental values. Also, we demonstrated that multiple layer regulations play a major role in shifting a central metabolism.

九州工業大学博士学位論文 学位記番号:情工博甲第318号 学位授与年月日:平成29年3月24日

1 Introduction|2 Background|3 Methodology|4 Results and Discussions|5 Conclusion and Future Research Interest

平成28年度

九州工業大学博士学位論文(要旨)学位記番号:情工博甲第318号 学位授与年月日:平成29年3月24日

目次

  1. 2017-10-02 再収集 / (index.pdf)

キーワード

Transcription factor, Systems Modeling, Integrated Dynamic Model, Enzyme Activity, Systems Behavior, Allosteric Regulation

各種コード

NII論文ID(NAID)

500001036623

NII著者ID(NRID)
  • 8000001129899
本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

外部リンク

博士論文 / 九州工業大学 / 情報工学

博士論文 / 九州工業大学

博士論文 / 情報工学

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