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    • 2. 发明申请
    • METHOD FOR ANALYZING METABOLITES FLUX USING CONVERGING RATIO DETERMINANT AND SPLIT RATIO DETERMINANT
    • 使用合并比例测定仪和分离比例测定仪分析代谢物通量的方法
    • WO2007123295A1
    • 2007-11-01
    • PCT/KR2006/003578
    • 2006-09-08
    • KOREAN ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYLEE, Sang YupCHOI, Hyung SeokKIM, Tae Yong
    • LEE, Sang YupCHOI, Hyung SeokKIM, Tae Yong
    • G01N33/50
    • G01N33/5088G01N2333/245
    • The present invention relates to a method for analyzing metabolic flux using CRD and SRD. Specifically, the method comprising: selecting a specific target organism, constructing the metabolic network model of the selected organism, identifying the correlations between specific metabolic fluxes in the metabolic network model, defining the correlation ratios as CRD and SRD, determining the correlation ratios of the metabolic fluxes through the experiment for measuring metabolic flux ratios, modifying a stoichiometric matrix with the determined CRD, SRD and correlation ratios, and applying the modified stoichiometric matrix of the metabolic network model for linear programming. According to the inventice method, the correlation between influent/effluent metabolic fluxes with respect to specific metabolites in target organisms (including E. coli ), the genome-scale metabolic network model of which was constructed, can be determined as relative ratio using useful information obtained from various experiments, including a growth experiment using a radioactive isotope-labeled carbon source and an assay for measuring enzymatic reaction. Thus, limit values from various experiments can be effectively applied, so that internal metabolic flux can be quantified and analyzed in a more accurate and rapid manner.
    • 本发明涉及使用CRD和SRD分析代谢通量的方法。 具体而言,该方法包括:选择特定目标生物体,构建所选生物体的代谢网络模型,识别代谢网络模型中特定代谢通量之间的相关性,将相关比定义为CRD和SRD,确定相关比例 通过用于测量代谢通量比的实验的代谢通量,用确定的CRD,SRD和相关比改变化学计量矩阵,并应用用于线性规划的代谢网络模型的修改的化学计量矩阵。 根据发明方法,可以使用有用的信息来确定其基因组尺度代谢网络模型被构建的目标生物体(包括大肠杆菌)中特定代谢物的流入/排出代谢通量之间的相关性 从各种实验中获得,包括使用放射性同位素标记的碳源的生长实验和用于测量酶反应的测定。 因此,可以有效地应用各种实验的极限值,从而能够以更准确和快速的方式量化和分析内部代谢通量。
    • 3. 发明申请
    • METHOD OF IN-SILICO IMPROVEMENT OF ORGANISMS USING THE FLUX SUM OF METABOLITES
    • 使用代谢物通量的有机硅改善方法
    • WO2007007933A1
    • 2007-01-18
    • PCT/KR2005/003442
    • 2005-10-14
    • KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYLEE, Sang YupKIM, Tae YongLEE, Dong Yup
    • LEE, Sang YupKIM, Tae YongLEE, Dong Yup
    • C12Q1/68
    • G06F19/12G06F19/18
    • The present invention relates to an in silico method for improving an organism on the basis of the flux sum (Φ) of metabolites, and more particularly to a method for screening key metabolites that increase the production yield of a useful substance, the method comprising defining the metabolite utilization of an organism for producing a useful substance as flux sum and perturbing the flux sum, as well as a method for improving an organism producing a useful substance, the method comprising deleting and/or amplifying genes associated with the aforementioned screened key metabolites. According to the present invention, the correlation between specific metabolites and useful substance production can be exactly predicted, so that it is possible to develop an organism having increased useful substance production by introducing and/or amplifying and/or deleting genes expressing enzymes associated with the specific metabolites. In addition, it is also possible to increase the production of a useful substance by adding specific metabolites during culture.
    • 本发明涉及一种用于基于代谢物的通量和(F)改善生物体的计算机方法,更具体地涉及一种用于筛选提高有用物质的产量的关键代谢物的方法,所述方法包括定义 用于产生有用物质的生物体的代谢物利用作为助熔剂和扰乱通量和,以及改善产生有用物质的生物体的方法,所述方法包括删除和/或扩增与上述筛选的关键代谢物相关的基因 。 根据本发明,可以准确地预测特定代谢物和有用物质生产之间的相关性,从而可以通过引入和/或扩增和/或删除表达与...相关的酶的基因来开发具有增加的有用物质生产的生物体 特异性代谢物。 此外,还可以通过在培养期间加入特定的代谢物来增加有用物质的产生。
    • 7. 发明申请
    • METHOD FOR SCREENING ESSENTIAL METABOLITES IN GROWTH OF MICROORGANISMS
    • 筛选微生物生长中基本代谢物的方法
    • WO2008078911A1
    • 2008-07-03
    • PCT/KR2007/006708
    • 2007-12-21
    • KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYLEE, Sang YupJEONG, HawoongKIM, Tae YongKIM, Pan-JunLEE, Kwang Ho
    • LEE, Sang YupJEONG, HawoongKIM, Tae YongKIM, Pan-JunLEE, Kwang Ho
    • G01N33/48
    • C12Q1/18G01N33/5038
    • The present invention disclosed is a method for screening metabolites essential for the growth of microorganism using metabolic flux analysis. More specifically, the present invention relates to the method for screening metabolites essential for the growth of microorganism, by selecting a target microorganism, constructing a metabolic network model of the selected microorganism, inactivating the consumption reaction of each of metabolites in the constructed metabolic network model, analyzing the metabolic flux of the metabolites to select metabolites essential for the growth of the microorganism, and confirming the selected metabolites using the utilization of each of the metabolites, defined as flux sum (Φ ). According to the present invention, metabolites essential for the growth of microorganism, and genes involved in the essential metabolites, can be screened in a convenient manner, and drug-target genes against pathogenic microorganisms can be predicted by deleting genes associated with the metabolites screened according to the method.
    • 所公开的本发明是使用代谢通量分析来筛选微生物生长所必需的代谢物的方法。 更具体地说,本发明涉及通过选择靶微生物,构建所选择的微生物的代谢网络模型,在构建的代谢网络模型中灭活各代谢物的消耗反应来筛选微生物生长所必需的代谢物的方法 分析代谢物的代谢通量以选择对微生物生长至关重要的代谢物,并使用定义为通量(F)的每种代谢物来确认所选择的代谢物。 根据本发明,可以以便利的方式筛选微生物生长所必需的代谢物和基本代谢物所涉及的基因,并且可以通过删除与代谢物相关的基因来预测针对病原微生物的药物靶基因 的方法。
    • 8. 发明申请
    • METHOD FOR IMPROVING A STRAIN BASED ON IN-SILICO ANALYSIS
    • 用于改进基于硅分析的应变的方法
    • WO2006107127A1
    • 2006-10-12
    • PCT/KR2005/001501
    • 2005-05-23
    • KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYLEE, Sang YupKIM, Tae YongLEE, Dong YupLEE, Sang Jun
    • LEE, Sang YupKIM, Tae YongLEE, Dong YupLEE, Sang Jun
    • C12N1/00
    • C12P7/46C12N9/1205C12N15/1089
    • The present invention is related to a method for improving a strain on the basis of in silico analysis, in which it compares the genomic information of a target strain for producing a useful substance to the genomic information of a strain overproducing the useful substance so as to primarily screen genes unnecessary for the overproduction of the useful substance, and then to secondarily screen genes to be deleted through performing simulation with metabolic flux analysis. According to the present invention, an improved strain can be effectively constructed by the metabolic and genetic engineering approach comprising comparatively analyzing the genomic information of a target strain for producing a useful substance and the genomic information of a strain producing a large amount of the useful substance to screen candidate genes and performing in silico simulation on the screened candidate genes to select a combination of genes to be deleted, which shows an improvement in the production of the useful substance. Accordingly, the time, effort and cost required for an actual wet test can be significantly reduced.
    • 本发明涉及一种基于在计算机分析中改进菌株的方法,其中将用于产生有用物质的靶菌株的基因组信息与过量产生有用物质的菌株的基因组信息进行比较,以便 主要是用于过量生产有用物质的筛选基因,然后通过用代谢通量分析进行模拟来次要筛选待缺失的基因。 根据本发明,可以通过代谢和基因工程方法有效地构建改进的菌株,其包括比较分析用于产生有用物质的靶菌株的基因组信息和产生大量有用物质的菌株的基因组信息 筛选候选基因并在筛选的候选基因的计算机模拟中进行选择要缺失的基因的组合,其显示有用物质的生产的改善。 因此,可以显着降低实际湿测试所需的时间,精力和成本。
    • 9. 发明申请
    • METHOD OF IMPROVEMENT OF ORGANISMS USING PROFILING THE FLUX SUM OF METABOLITES
    • 使用分析代谢物的通量来改善有机体的方法
    • WO2007129793A1
    • 2007-11-15
    • PCT/KR2006/003576
    • 2006-09-08
    • KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGYLEE, Sang YupKIM, Tae YongLEE, Dong-Yup
    • LEE, Sang YupKIM, Tae YongLEE, Dong-Yup
    • G01N33/50
    • G06F19/12G01N33/5088
    • The present invention relates to a method for improving an organism through the profiling of flux sum of metabolites, and more particularly to a method for screening key metabolites, the method comprises: plotting a profile between objective functions based on useful substance formation rate as a main function through an algorithm perturbing other functions influencing the production of useful substance; determining the utilization (flux sum (Φ )) of all metabolites from the profile; and screening key metabolites, which show an increase in flux sum (Φ ) with an increase in useful substance formation rate. The present invention also relates to a method for improving an organism producing a useful substance, the method comprises introducing and/or amplifying genes associated with the screened key metabolites or introducing the genes from the outside into the organism. According to the disclosed invention, the metabolic utilization (flux sum; Φ) of specific metabolites according to an increase in useful substance formation rate can be predicted, so that key metabolites in increasing the production of a useful substance can be screened. Also, it is possible to increase the production of a useful substance through the method of improving a target organism by introducing and/or amplifying genes associated with the screened metabolites or through the method of supplying the metabolites during the culture of the organism.
    • 本发明涉及一种通过对代谢物的助熔剂总量进行分析来改善生物体的方法,更具体地涉及筛选关键代谢物的方法,该方法包括:基于有用的物质形成速率作为主要目标函数绘制轮廓 通过扰乱影响有用物质生产的其他功能的算法的功能; 确定所有代谢物从轮廓中的利用率(通量(F)); 并筛选关键代谢物,随着有用物质形成率的增加,其表现出助熔剂总量(F)的增加。 本发明还涉及一种改善产生有用物质的生物体的方法,所述方法包括引入和/或扩增与筛选的关键代谢物相关的基因或将基因从外部引入生物体。 根据所公开的发明,可以预测根据有用物质形成速率的增加的特定代谢物的代谢利用(助剂和F),从而可以筛选出增加有用物质生产的关键代谢物。 此外,可以通过引入和/或扩增与筛选的代谢物相关的基因或通过在生物体培养期间提供代谢物的方法来改善靶生物体的方法来增加有用物质的产生。