SCI和EI收录∣中国化工学会会刊

Chinese Journal of Chemical Engineering ›› 2012, Vol. 20 ›› Issue (5): 958-970.

• • 上一篇    下一篇

Nonlinear Mathematical Simulation and Analysis of Dha Regulon for Glycerol Metabolism in Klebsiella pneumoniae*

孙亚琴1, 叶剑雄2, 牟晓佳1, 滕虎1, 冯恩民2, 曾安平3, 修志龙1   

  1. 1. Department of Bioscience & Biotechnology, Dalian University of Technology, Dalian 116024, China;
    2. Department of Applied Mathematics, Dalian University of Technology, Dalian 116024, China;
    3. Institute of Bioprocess and Biochemical Engineering, Technical University of Hamburg-Harburg, D-21073 Hamburg, Germany
  • 收稿日期:2011-03-30 修回日期:2011-07-01 出版日期:2012-10-28 发布日期:2012-11-06
  • 通讯作者: XIU Zhilong,E-mail:zhlxiu@dlut.edu.cn
  • 基金资助:
    Supported by the National High Technology Research and Development Program of China (2007AA02Z208);the State Key Development Program for Basic Research of China (2007CB714304)

Nonlinear Mathematical Simulation and Analysis of Dha Regulon for Glycerol Metabolism in Klebsiella pneumoniae*

SUN Yaqin1, YE Jianxiong2, MU Xiaojia1, TENG Hu1, FENG Enmin2, ZENG Anping3, XIU Zhilong1   

  1. 1. Department of Bioscience & Biotechnology, Dalian University of Technology, Dalian 116024, China;
    2. Department of Applied Mathematics, Dalian University of Technology, Dalian 116024, China;
    3. Institute of Bioprocess and Biochemical Engineering, Technical University of Hamburg-Harburg, D-21073 Hamburg, Germany
  • Received:2011-03-30 Revised:2011-07-01 Online:2012-10-28 Published:2012-11-06
  • Supported by:
    Supported by the National High Technology Research and Development Program of China (2007AA02Z208);the State Key Development Program for Basic Research of China (2007CB714304)

摘要: Glycerol may be converted to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae under anaerobic conditions and glycerol dismutation involves two parallel pathways controlled by the dha regulon. In this study, a fourteen-dimensional nonlinear dynamic system is presented to describe the continuous culture and multiplicity analysis, in which two regulated negative-feedback mechanisms of repression and enzyme inhibition are investigated. The model describing the expression of gene-mRNA-enzyme-product was established according to the repression of the dha regulon by 3-hydroxypropionaldehy (3-HPA). Comparisons between simulated and experimental results indicate that the model can be used to describe the production of 1,3-PD under continuous fermentation. The new model is translated into the corresponding S-system version. The robustness of this model is discussed by using the S-system model and the sensitivity analysis shows that the model is sufficiently robust. The influences of initial glycerol concentration and dilution rate on the biosynthesis of 1,3-PD and the stability of the dha regulon model are investigated. The intracellular concentrations of glycerol, 1,3-PD, 3-HPA, repressor mRNA, repressor, mRNA and protein levels of glycerol dehydratase (GDHt) and 1,3-PD oxydoreductase (PDOR) can be predicted for continuous cultivation. The results of simulation and analysis indicate that 3-HPA accumulation will repress the expression of the dha regulon at the transcriptional level. This model gives new insights into the regulation of glycerol metabolism in K. pneumoniae and explain some of the experimental observations.

关键词: dha regulon, robustness, nonlinear dynamics, genetic regulation, 3-hydroxypropionaldehy

Abstract: Glycerol may be converted to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae under anaerobic conditions and glycerol dismutation involves two parallel pathways controlled by the dha regulon. In this study, a fourteen-dimensional nonlinear dynamic system is presented to describe the continuous culture and multiplicity analysis, in which two regulated negative-feedback mechanisms of repression and enzyme inhibition are investigated. The model describing the expression of gene-mRNA-enzyme-product was established according to the repression of the dha regulon by 3-hydroxypropionaldehy (3-HPA). Comparisons between simulated and experimental results indicate that the model can be used to describe the production of 1,3-PD under continuous fermentation. The new model is translated into the corresponding S-system version. The robustness of this model is discussed by using the S-system model and the sensitivity analysis shows that the model is sufficiently robust. The influences of initial glycerol concentration and dilution rate on the biosynthesis of 1,3-PD and the stability of the dha regulon model are investigated. The intracellular concentrations of glycerol, 1,3-PD, 3-HPA, repressor mRNA, repressor, mRNA and protein levels of glycerol dehydratase (GDHt) and 1,3-PD oxydoreductase (PDOR) can be predicted for continuous cultivation. The results of simulation and analysis indicate that 3-HPA accumulation will repress the expression of the dha regulon at the transcriptional level. This model gives new insights into the regulation of glycerol metabolism in K. pneumoniae and explain some of the experimental observations.

Key words: dha regulon, robustness, nonlinear dynamics, genetic regulation, 3-hydroxypropionaldehy