【作者】 张作阳；

【导师】 张旭；

【作者基本信息】 大连理工大学 ， 运筹学与控制论， 2010， 硕士

【摘要】 本文以微生物歧化甘油生产1,3-丙二醇(1,3-PD)连续发酵过程为背景,研究三羟基丙醛(3-HPA)对甘油脱水酶(PDHt)和1,3-丙二醇氧化还原酶(PDOR)的活性抑制作用。在假设3-HPA对细胞比生长速率无抑制作用及甘油、1.3-PD跨膜运输方式为主被动结合运输的条件下,建立混杂非线性动力学模型,并研究了模型的基本性质。为了推断3-HPA对两种关键酶是否有抑制作用及抑制作用区域,提出了混杂非线性动力系统的定量鲁棒性分析方法。并基于鲁棒性指标,建立混杂非线性动力系统辨识模型,通过数值计算推断出了3-HPA对这两种酶的抑制作用区域。本课题受国家自然科学基金项目“一类复杂网络上非光滑动力系统的优化理论与算法”(编号为10871033)和国家高技术研究发展计划(863计划)“生物柴油与1,3-丙二醇联产工艺优化研究”(编号为2007AA02Z208)的资助。此项目研究将为实现1,3-PD的产业化生产提供理论指导,具有重要的理论意义与应用价值。本论文的研究内容与得到的主要结果可概括如下：1.在甘油连续发酵生产1,3-PD过程中,针对3-HPA对两种关键酶活性抑制作用的不同情形,在假设3-HPA对细胞比生长速率无抑制作用及甘油、1.3-PD跨膜运输方式为主被动结合运输条件下,建立了混杂非线性动力系统,并证明了动力系统解的存在唯一性及解关于参量的连续依赖性。2.针对细胞内物质浓度无法测量问题,提出了生物系统鲁棒性的定量分析方法。以细胞外物质浓度的计算值与实验值的相对误差及生物鲁棒性作为性能指标,混杂非线性动力系统和系统的近似稳态性为主要约束,建立了具有离散和连续参量的混杂非线性动力系统辨识模型,并证明了该模型的可辨识性。最后构造优化算法,并通过数值计算推断出了3-HPA对PDHt酶和PDOR酶的抑制作用区域。更多还原

【Abstract】 The continuous fermentation of bio-dissimilation of glycerol to 1,3-propane-diol (1,3-PD) by Klebsiella pneumoniae(K.pneumoniae) are investigated in this paper. based on the different cases on the inhibitions of 3-hydroxypropionaldehyde (3-HPA) to the effect activities of two key enzymes (glycerol dehydratase (GDHt)and 1,3-propanediol oxydore-ductase (PDOR)), a nonlinear hybrid dynamical system is proposed on the hypothesis that the glycerol and 1,3-PD pass the cell membrane by both passive diffusion and active transport and that there is no inhibition of 3-HPA to the specific growth rate of cells. And the fundamental properties of the system are investigated. To infer the most rea-sonable case, a quantitative definition of biological robustness is presented. Taking the presented biological robustness as performance index, a system identification model is established. Finally, we obtain the most reasonable system to describe the inhibition of 3-HPA to the two key enzymes and compute the range of inhibition of 3-HPA to the two enzymes by numerical computation.This work was supported by National Natural Sci-ence Foundation "Optimization theory and algorithm of nonsmooth dynamic system in a class of complex networks" (No.10871033) and the National High Technology Research and Development Program(863 Program) "Biodiesel and 1,3-Propanediol Integrated Pro-duction"(No.2007AA02Z208). The main results obtained in this dissertation may be summarized as follows:1. During the continuous culture of glycerol bioconversion to 1.3-PD, based on the cases whether the inhibitions of 3-HPA to the effect activities of two key enzymes ( GDHt and PDOR), we propose a nonlinear hybrid dynamical system on the hypothesis that the glycerol and 1,3-PD pass the cell membrane by both passive diffusion and active transport and that there is no inhibition of 3-HPA to the specific growth rate of cells. And the fundamental properties of the system are investigated:the existence and uniqueness of the solution to the system and the continuous dependent with respect to parameters.2. Because of the lack of intracellular information, we propose a quantitative defini-tion of biological robustness. taking the average relative error of extracellular substance concentrations and the biological robustness as performance index, we establish an iden-tification model containing discrete and continuous parameters, which is subject to some conditions including the proposed nonlinear hybrid dynamical systems and the approxi- matelv steady state of the dynamical system. Subsequently, we prove the identifiability of the model. Finally, we obtain the range of inhibition of 3-HPA to the two enzymes by numerical computation.更多还原