Simulation Study of Dynamic Network Model for L-Threonine Biosynthesis in Escherichia coli

대장균의 동역학 네트워크 모델을 이용한 L-threonine 생합성에 관한 모사 연구

  • Jung, Uisub (Department of Chemical and Biomolecular Engineering, Sogang University) ;
  • Lee, Jinwon (Department of Chemical and Biomolecular Engineering, Sogang University)
  • 정의섭 (서강대학교 화공생명공학과) ;
  • 이진원 (서강대학교 화공생명공학과)
  • Received : 2006.01.12
  • Accepted : 2006.02.03
  • Published : 2006.02.28

Abstract

In order to investigate the effect of inhibitors on L-threonine biosynthesis in Escherichia coli, we have constructed a metabolic network model of amino acid biosynthesis from L-aspartate to L-threonine by using available informations from literatures and databases. In the model, the effects of inhibitors on the biosynthesis of L-threonine was included as an appropriate mathematical form. For simulation study, we used initial values as L-aspartate 5 mM, ATP 5 mM, NADPH 2 mM, and observed the concentration changes of intermediate metabolites over concentration changes of respective inhibitors. As a result, we found that concentrations of intermediate metabolites were not significantly changed over concentration changes of L-lysine, L-methionine, and L-glutamate. But, there were considerable changes of intermediates over concentration changes of L-serine, L-cysteine, and L-threonine, which can be considered as essential effectors on L-threonine synthesis. Contrary, the synthesis of L-threonine seems to be not related to the amounts of L-aspartate, and inversely proportional to the accumulated amount of D,L-aspartic ${\beta}$-semialdehyde.

본 연구에서는 대장균 내에서 L-threonine의 생합성에 영향을 미치는 저해제들에 대한 모사 연구를 위하여 L-aspartate에서 L-threonine까지의 아미노산 생합성 대사 네트워크를 문헌 및 데이터베이스를 통해 구축하였다. 또한 L-threonine 생합성에 영향을 미치는 저해제들을 수학적으로 모델링하여 효소 반응식에 적용시켰다. 모사 연구를 위해 초기 농도값을 L-aspartate 5 mM, ATP 5 mM, NADPH 2 mM으로 설정하고 저해제의 농도 변화에 따른 세포내 대사 물질들의 농도변화를 확인하였다. 그 결과 저해제 L-lysine, L-methionine, L-glutamate는 저해제 농도 변화에 따라 대사 물질들의 농도 변화가 없었다. 그러나 저해제 L-serine, L-cysteine 그리고 L-threonine의 경우 저해제의 농도 변화에 따라 세포내 대사물질들의 농도 곡선이 서로 다른 결과를 얻었다. 대장균 내에서 소비되어진 L-aspartate의 농도는 세포 내 생성되는 L-threonine과는 관련이 없었고, 생성되는 L-threonine의 농도는 세포 내에 축적된 D,L-aspartic ${\beta}$-semialdehyde에 반비례하였다.

Keywords

Acknowledgement

Supported by : 과학기술부

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