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1. 发明授权

US08852898B2 L-threonine overproducing microorganism and method for preparing L-threonine using the same 有权
标题翻译： L-苏氨酸过量生产微生物和使用其制备L-苏氨酸的方法
公开(公告)号：US08852898B2
公开(公告)日：2014-10-07
申请号：US12160126
申请日：2007-07-02
申请人： Sang Yup Lee , Kwang Ho Lee , Jin Hwan Park , Tae Yong Kim
发明人： Sang Yup Lee , Kwang Ho Lee , Jin Hwan Park , Tae Yong Kim
IPC分类号： C12P13/08
CPC分类号： C12P13/08
摘要： The present invention relates to a mutant microorganism producing a high concentration of L-threonine in high yield, prepared using site-specific mutation, not random mutation, such as treatment with a mutation inducer, a method for preparing the same, and a method for preparing L-threonine using the mutant microorganism producing L-threonine. By using the mutant microorganism according to the present invention, L-threonine can be prepared at high yield, additional strain development becomes possible and their physiological phenomena can be easily understood since genetic information of L-threonine producing microorganism can be identified.
摘要翻译：本发明涉及使用位点特异性突变而不是任意突变（例如用突变诱导剂处理）制备高产量的L-苏氨酸的高浓度的突变型微生物，其制备方法和使用产生L-苏氨酸的突变体微生物制备L-苏氨酸。通过使用根据本发明的突变微生物，可以高产率制备L-苏氨酸，由于可以鉴定L-苏氨酸生产微生物的遗传信息，所以可以进行附加应变发展，并且可以容易地理解其生理现象。

2. 发明授权

US08148137B2 Mutant microorganism having improved production ability of branched amino acid and method for preparing branched amino acid using the same 有权
标题翻译：具有提高支链氨基酸生产能力的突变体微生物及使用其制备支链氨基酸的方法
公开(公告)号：US08148137B2
公开(公告)日：2012-04-03
申请号：US12097099
申请日：2007-03-14
申请人： Sang Yup Lee , Jin Hwan Park , Kwang Ho Lee , Tae Yong Kim
发明人： Sang Yup Lee , Jin Hwan Park , Kwang Ho Lee , Tae Yong Kim
IPC分类号： C12N1/21 , C12P13/08
CPC分类号： C12P13/08 , C12N9/1014 , C12Y201/02011
摘要： The present invention relates to mutant microorganisms having improved productivity of branched-chain amino acids, and a method for producing branched-chain amino acids using the mutant microorganisms. More specifically, relates to mutant microorganisms having improved productivity of L-valine, which are produced by attenuating or deleting a gene encoding an enzyme involved in L-isoleucine biosynthesis, a gene encoding an enzyme involved in L-leucine, and a gene encoding an enzyme involved in D-pantothenic acid biosynthesis, and mutating a gene encoding an enzyme involved in L-valine biosynthesis, such that the expression thereof is increased, as well as a method for producing L-valine using the mutant microorganisms. The inventive mutant microorganisms produced by site-specific mutagenesis and metabolic pathway engineering can produce branched-chain amino acids, particularly L-valine, with high efficiency, and thus will be useful as industrial microorganisms for producing L-valine.
摘要翻译：本发明涉及具有提高的支链氨基酸生产率的突变微生物，以及使用突变微生物生产支链氨基酸的方法。更具体地，涉及通过减弱或缺失编码参与L-异亮氨酸生物合成的酶的基因，编码L-亮氨酸的酶的基因和编码L-亮氨酸的基因而产生的L-缬氨酸的生产率提高的突变体微生物涉及D-泛酸生物合成的酶，以及编码参与L-缬氨酸生物合成的酶的基因的突变，使得其表达增加，以及使用突变微生物产生L-缬氨酸的方法。通过位点特异性诱变和代谢途径工程产生的本发明的突变体微生物可以高效地产生支链氨基酸，特别是L-缬氨酸，因此可用作生产L-缬氨酸的工业微生物。

3. 发明申请

US20110003349A1 L-Threonine Overproducing Microorganism and Method for Preparing L-Threonine Using the Same 有权
标题翻译： L-苏氨酸过量生产微生物及使用其制备L-苏氨酸的方法
公开(公告)号：US20110003349A1
公开(公告)日：2011-01-06
申请号：US12160126
申请日：2007-07-02
申请人： Sang Yup Lee , Kwang Ho Lee , Jin Hwan Park , Tae Yong Kim
发明人： Sang Yup Lee , Kwang Ho Lee , Jin Hwan Park , Tae Yong Kim
IPC分类号： C12P13/08 , C12N15/63 , C12N1/21 , C12N1/15 , C12N1/19
CPC分类号： C12P13/08
摘要： The present invention relates to a mutant microorganism producing a high concentration of L-threonine in high yield, prepared using site-specific mutation, not random mutation, such as treatment with a mutation inducer, a method for preparing the same, and a method for preparing L-threonine using the mutant microorganism producing L-threonine. By using the mutant microorganism according to the present invention, L-threonine can be prepared at high yield, additional strain development becomes possible and their physiological phenomena can be easily understood since genetic information of L-threonine producing microorganism can be identified.
摘要翻译：本发明涉及使用位点特异性突变而不是任意突变（例如用突变诱导剂处理）制备高产量的L-苏氨酸的高浓度的突变型微生物，其制备方法和使用产生L-苏氨酸的突变体微生物制备L-苏氨酸。通过使用根据本发明的突变微生物，可以高产率制备L-苏氨酸，由于可以鉴定L-苏氨酸生产微生物的遗传信息，所以可以进行附加应变发展，并且可以容易地理解其生理现象。

4. 发明申请

US20090053779A1 MUTANT MICROORGANISM HAVING IMPROVED PRODUCTION ABILITY OF BRANCHED AMINO ACID AND METHOD FOR PREPARING BRANCHED AMINO ACID USING THE SAME 有权
标题翻译：具有改进的分支氨基酸生产能力的突变微生物及使用其制备分支氨基酸的方法
公开(公告)号：US20090053779A1
公开(公告)日：2009-02-26
申请号：US12097099
申请日：2007-03-14
申请人： Sang Yup Lee , Jin Hwan Park , Kwang Ho Lee , Tae Yong Kim
发明人： Sang Yup Lee , Jin Hwan Park , Kwang Ho Lee , Tae Yong Kim
IPC分类号： C12P13/08 , C12N15/01 , C12N15/80 , C12N15/81 , C12N15/74 , C12N1/14 , C12N1/15 , C12N1/16 , C12N1/19 , C12N1/20 , C12N1/21
CPC分类号： C12P13/08 , C12N9/1014 , C12Y201/02011
摘要： The present invention relates to mutant microorganisms having improved productivity of branched-chain amino acids, and a method for producing branched-chain amino acids using the mutant microorganisms. More specifically, relates to mutant microorganisms having improved productivity of L-valine, which are produced by attenuating or deleting a gene encoding an enzyme involved in L-isoleucine biosynthesis, a gene encoding an enzyme involved in L-leucine, and a gene encoding an enzyme involved in D-pantothenic acid biosynthesis, and mutating a gene encoding an enzyme involved in L-valine biosynthesis, such that the expression thereof is increased, as well as a method for producing L-valine using the mutant microorganisms. The inventive mutant microorganisms produced by site-specific mutagenesis and metabolic pathway engineering can produce branched-chain amino acids, particularly L-valine, with high efficiency, and thus will be useful as industrial microorganisms for producing L-valine.
摘要翻译：本发明涉及具有提高的支链氨基酸生产率的突变微生物，以及使用突变微生物生产支链氨基酸的方法。更具体地，涉及通过减弱或缺失编码参与L-异亮氨酸生物合成的酶的基因，编码L-亮氨酸的酶的基因和编码L-亮氨酸的基因而产生的L-缬氨酸的生产率提高的突变体微生物涉及D-泛酸生物合成的酶，以及编码参与L-缬氨酸生物合成的酶的基因的突变，使得其表达增加，以及使用突变微生物产生L-缬氨酸的方法。通过位点特异性诱变和代谢途径工程产生的本发明的突变体微生物可以高效地产生支链氨基酸，特别是L-缬氨酸，因此可用作生产L-缬氨酸的工业微生物。

5. 发明申请

US20100143911A1 METHOD FOR SCREENING ESSENTIAL METABOLITES IN GROWTH OF MICROORGANISMS 有权
标题翻译：筛选微生物生长中基本代谢物的方法
公开(公告)号：US20100143911A1
公开(公告)日：2010-06-10
申请号：US12519791
申请日：2007-12-21
申请人： Sang Yup Lee , Hawoong Jeong , Tae Yong Kim , Pan-Jun Kim , Kwang Ho Lee
发明人： Sang Yup Lee , Hawoong Jeong , Tae Yong Kim , Pan-Jun Kim , Kwang Ho Lee
IPC分类号： C12Q1/68 , C12Q1/02 , C12N15/74 , C12N1/21
CPC分类号： C12Q1/18 , G01N33/5038
摘要： 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.
摘要翻译：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费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微生物生长所必需的代谢物，并使用定义为通量和（Φ）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。

6. 发明授权

US08494779B2 Method for screening essential metabolites in growth of microorganisms 有权
标题翻译：筛选微生物生长中重要代谢物的方法
公开(公告)号：US08494779B2
公开(公告)日：2013-07-23
申请号：US12519791
申请日：2007-12-21
申请人： Sang Yup Lee , Hawoong Jeong , Tae Yong Kim , Pan-Jun Kim , Kwang Ho Lee
发明人： Sang Yup Lee , Hawoong Jeong , Tae Yong Kim , Pan-Jun Kim , Kwang Ho Lee
IPC分类号： G06F19/10 , G06F19/12
CPC分类号： C12Q1/18 , G01N33/5038
摘要： 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.
摘要翻译：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费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于微生物生长至关重要的代谢物，并且使用定义为通量总和（Phi）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。

7. 发明授权

US07752540B2 Information system for metabolic flux analysis using extensible markup language and operating method thereof 失效
标题翻译：使用可扩展标记语言进行代谢通量分析的信息系统及其操作方法
公开(公告)号：US07752540B2
公开(公告)日：2010-07-06
申请号：US11148907
申请日：2005-06-09
申请人： Sang Yup Lee , Hong Seok Yun , Dong Yup Lee , Seung Hyun Lee , Joon Woo Jeong , Tae Yong Kim
发明人： Sang Yup Lee , Hong Seok Yun , Dong Yup Lee , Seung Hyun Lee , Joon Woo Jeong , Tae Yong Kim
IPC分类号： G06F17/00
CPC分类号： G06F19/26 , G06F19/12
摘要： The present invention relates to an MFA (Metabolic Flux Analysis) information system using an XML (eXtensible Markup Language) and an operating method thereof. More specifically, the invention relates to an MFA information system and an operating method thereof, which generates, edits, stores and visualizes an MFA model feature and an MFA object using XML, and edits, stores and visualizes the result obtained by performing MFA based on the object. The present invention provides the MFA information system and method capable of generating, editing, storing and visualizing MFA model features and MFA objects using XML. Accordingly, MFA can be easily performed by utilizing advantages of XML, such as transplantation, reusability, deciphering, scalability, flexibility and effective data exchange, and thus the present invention can be applied to cell improvement using metabolic engineering.
摘要翻译：本发明涉及使用XML（可扩展标记语言）的MFA（代谢通量分析）信息系统及其操作方法。更具体地，本发明涉及一种MFA信息系统及其操作方法，其使用XML生成，编辑，存储和可视化MFA模型特征和MFA对象，并且通过执行MFA获得的结果进行编辑，存储和可视化物体。本发明提供了能够使用XML来生成，编辑，存储和可视化MFA模型特征和MFA对象的MFA信息系统和方法。因此，通过利用移植，可重用性，解密，可扩展性，灵活性和有效的数据交换等XML的优点，可以容易地实现MFA，因此本发明可以应用于使用代谢工程的细胞改良。

8. 发明申请

US20090215048A1 METHOD OF IN-SILICO IMPROVEMENT OF ORGANISMS USING THE FLUX SUM OF METABOLITES 审中-公开
标题翻译：使用代谢物通量的有机硅改善方法
公开(公告)号：US20090215048A1
公开(公告)日：2009-08-27
申请号：US11994330
申请日：2005-10-14
申请人： Sang Yup Lee , Tae Yong Kim , Dong Yup Lee
发明人： Sang Yup Lee , Tae Yong Kim , Dong Yup Lee
IPC分类号： C12Q1/68 , G06F19/00 , C12N15/00 , C12N15/74 , C12P7/46
CPC分类号： G16B5/00 , G16B20/00
摘要： 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.
摘要翻译：本发明涉及一种基于代谢物的通量和（phi）改善生物体的计算机方法，更具体地涉及一种筛选提高有用物质产量的关键代谢物的方法，该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。

9. 发明申请

US20090075352A1 Method For Improving A Strain Based On In-Silico Analysis 审中-公开
标题翻译：基于硅胶分析改进应变的方法
公开(公告)号：US20090075352A1
公开(公告)日：2009-03-19
申请号：US11722632
申请日：2005-05-23
申请人： Sang Yup Lee , Tae Yong Kim , Dong Yup Lee , Sang Jun Lee
发明人： Sang Yup Lee , Tae Yong Kim , Dong Yup Lee , Sang Jun Lee
IPC分类号： C12P7/46 , G06G7/48 , C12N1/21
CPC分类号： C12P7/46 , C12N9/1205 , C12N15/1089
摘要： 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.
摘要翻译：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进。因此，可以显着降低实际湿测试所需的时间，精力和成本。

10. 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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