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。

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。

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。

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。

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。

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。

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。

公开(公告)号：US07803587B2

公开(公告)日：2010-09-28

申请号：US11743668

申请日：2007-05-02

申请人： Sang Yup Lee ,  Ho Nam Chang ,  Hyohak Song ,  Tae Yong Kim ,  Bo-Kyung Choi

发明人： Sang Yup Lee ,  Ho Nam Chang ,  Hyohak Song ,  Tae Yong Kim ,  Bo-Kyung Choi

IPC分类号： C12P7/44 ,  C12N1/20 ,  C12Q1/00 ,  C12Q1/68 ,  G06G7/48

CPC分类号： C12N1/20 ,  C12N5/0018 ,  C12N2500/32 ,  C12N2500/38 ,  C12N2500/40 ,  C12P7/46 ,  G06F19/12

摘要： A method for developing a culture medium using genome information and in silico analysis. In one implementation, the method involves developing a minimal synthetic medium, including the steps of constructing a metabolic network using genome information of prokaryotic cell or eukaryotic cell, selecting components of the minimal synthetic medium removing any one among external metabolites from the constructed metabolic network and conducting metabolic flux analysis using in silico simulation, and determining a final culture medium by actual culture.

摘要翻译： 使用基因组信息和计算机分析开发培养基的方法。 在一个实施方案中，该方法包括开发最小的合成培养基，包括使用原核细胞或真核细胞的基因组信息构建代谢网络的步骤，从构建的代谢网络中选择去除外部代谢物中的任何一种的最小合成培养基的组分，以及 使用计算机模拟进行代谢通量分析，并通过实际培养确定最终培养基。

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。

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。