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1. 发明授权

US08977530B2 Method for identifying genes for enhancing the production of useful substances 有权
标题翻译：识别用于增强有用物质生产的基因的方法
公开(公告)号：US08977530B2
公开(公告)日：2015-03-10
申请号：US11722709
申请日：2005-09-15
申请人： Sang Yup Lee , Han Min Woo , Hyung Seok Choi
发明人： Sang Yup Lee , Han Min Woo , Hyung Seok Choi
IPC分类号： G06G7/48 , G06F19/12
CPC分类号： G06F19/12
摘要： Provided is a method for improving useful substance-producing organisms using metabolic flux analysis, and more particularly a method for improving a host organism producing a useful substance, the method including: calculating a maximum flux value corresponding to the theoretical maximum yield of the useful substance in the metabolic network model of the host organism for producing useful substance, and calculating the optimum value of metabolic flux associated with useful substance production in the metabolic network when the value of cell growth-associated metabolic flux is the maximum under the condition where fermentation data are applied or not applied; selecting metabolic fluxes whose absolute values increase from the range between the maximum value and the optimum value; screening genes associated with the selected metabolic fluxes; and introducing and/or amplifying the selected genes in the host organism. Production of the useful substance can be effectively improved by using the method.
摘要翻译：本发明提供一种使用代谢通量分析改善有用的生物体生物的方法，更具体地说，涉及一种用于改善产生有用物质的宿主生物的方法，所述方法包括：计算与有用物质的理论最大产量相对应的最大通量值在用于生产有用物质的宿主生物体的代谢网络模型中，并且当在发酵数据的条件下细胞生长相关代谢通量的值最大时，计算与代谢网络中有用物质生产相关的代谢通量的最佳值被应用或不应用; 选择绝对值从最大值和最佳值之间的范围增加的代谢通量; 筛选与所选代谢通量相关的基因; 并引入和/或扩增宿主生物体中所选择的基因。可以通过使用该方法有效地改善有用物质的生产。

2. 发明申请

US20080220490A1 Method for Improving Organisms Using Flux Scanning Based on Enforced Objective Flux 有权
标题翻译：基于强化目标通量使用助焊剂扫描改善生物的方法
公开(公告)号：US20080220490A1
公开(公告)日：2008-09-11
申请号：US11722709
申请日：2005-09-15
申请人： Sang Yup Lee , Han Min Woo , Hyung Seok Choi
发明人： Sang Yup Lee , Han Min Woo , Hyung Seok Choi
IPC分类号： C12P5/02 , C12N1/21 , G06F17/10 , G06G7/60
CPC分类号： G06F19/12
摘要： The present invention relates to a method for improving useful substance-producing organisms using metabolic flux analysis, and more particularly to a method for improving a host organism producing a useful substance, the method comprising: calculating a maximum flux value corresponding to the theoretical maximum yield of the useful substance in the metabolic network model of the host organism for producing useful substance, and calculating the optimum value of metabolic flux associated with useful substance production in the metabolic network when the value of cell growth-associated metabolic flux is the maximum under the condition where fermentation data are applied or not applied; selecting metabolic fluxes whose absolute values increase from the range between the maximum value and the optimum value; screening genes associated with the selected metabolic fluxes; and introducing and/or amplifying the selected genes in the host organism. According to the invention, the production of the useful substance can be effectively improved by selecting metabolic fluxes to be amplified and genes involved in the metabolic fluxes from the range between the optimum value and maximum value of production-associated metabolic flux in the host organism for producing the useful substance, whose genome-level metabolic network model is constructed, and introducing and/or amplifying the selected genes in the organism.
摘要翻译：本发明涉及一种使用代谢通量分析改善有用的生物体生物的方法，更具体地说，涉及一种改善产生有用物质的宿主生物的方法，该方法包括：计算对应于理论最大产量的最大通量值的有用物质在宿主生物体的代谢网络模型中用于生产有用物质，并计算与代谢网络中有用物质生产相关的代谢通量的最佳值，当细胞生长相关代谢通量的值在应用或不应用发酵数据的条件; 选择绝对值从最大值和最佳值之间的范围增加的代谢通量; 筛选与所选代谢通量相关的基因; 并引入和/或扩增宿主生物体中所选择的基因。根据本发明，可以通过选择待扩增的代谢通量和代谢通量中涉及的基因从宿主生物中与生产相关的代谢通量的最佳值和最大值之间的范围内有效地提高有用物质的产生，产生其基因组级代谢网络模型构建的有用物质，以及引入和/或扩增生物体中所选择的基因。

3. 发明申请

US20090298070A1 METHOD FOR ANALYZING METABOLITES FLUX USING CONVERGING RATIO DETERMINANT AND SPLIT RATIO DETERMINANT 审中-公开
标题翻译：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
公开(公告)号：US20090298070A1
公开(公告)日：2009-12-03
申请号：US12297343
申请日：2006-09-08
申请人： Sang-Yup Lee , Hyung Seok Choi , Tae Yong Kim
发明人： Sang-Yup Lee , Hyung Seok Choi , Tae Yong Kim
IPC分类号： C12Q1/68 , C12Q1/02 , C12P19/34
CPC分类号： G01N33/5088 , G01N2333/245
摘要： 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.
摘要翻译：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。

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