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1. 发明授权

US09051552B2 Methods and organisms for utilizing synthesis gas or other gaseous carbon sources and methanol 有权
标题翻译：利用合成气或其他气态碳源和甲醇的方法和生物
公开(公告)号：US09051552B2
公开(公告)日：2015-06-09
申请号：US12875068
申请日：2010-09-02
申请人： Mark J. Burk , Christophe H. Schilling , Anthony P. Burgard , John D. Trawick
发明人： Mark J. Burk , Christophe H. Schilling , Anthony P. Burgard , John D. Trawick
IPC分类号： C12N9/20 , C12N9/10 , C12N9/02 , C12N9/00 , C12P19/32
CPC分类号： C12P7/18 , C12N9/0008 , C12N9/0036 , C12N9/1007 , C12N9/93 , C12N15/70 , C12P19/32 , Y02E50/343
摘要： The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, CO2 and/or H2 to acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or CO2 and H2 to acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. For example, the microbial organism can contain at least one exogenous nucleic acid encoding an enzyme or protein in an acetyl-CoA pathway. The microbial organism is capable of utilizing synthesis gases comprising CO, CO2 and/or H2, alone or in combination with methanol, to produce acetyl-CoA. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.
摘要翻译：本发明提供具有乙酰-CoA途径的非天然存在的微生物生物体，以及利用合成气或合成气和甲醇的能力。在一个实施方案中，本发明提供非天然存在的微生物，其包含一种或多种外源蛋白质，赋予微生物将CO，CO 2和/或H 2转化为乙酰辅酶A（乙酰辅酶A），甲基四氢叶酸（甲基 -THF）或其它所需产物，其中微生物缺乏在不存在一种或多种外源蛋白的情况下将CO或CO 2和H 2转化为乙酰辅酶A或甲基-THF的能力。例如，微生物生物体可以含有至少一种编码乙酰辅酶A途径中的酶或蛋白质的外源核酸。微生物生物能够单独或与甲醇组合使用包含CO，CO 2和/或H 2的合成气体，以产生乙酰辅酶A。本发明另外提供了生产乙酰辅酶A的方法，例如通过培养产生乙酰辅酶A的微生物，其中微生物生物体表达至少一种编码乙酰辅酶A途径酶或蛋白质的外源核酸，其量足够在条件下和足够的时间内产生乙酰辅酶A产生乙酰辅酶A。

2. 发明授权

US08949032B2 Multicellular metabolic models and methods 有权
公开(公告)号：US08949032B2
公开(公告)日：2015-02-03
申请号：US11188136
申请日：2005-07-21
申请人： Imandokht Famili , Christophe H. Schilling
发明人： Imandokht Famili , Christophe H. Schilling
IPC分类号： G01N33/50 , G06F19/12 , G06F19/18 , G06F19/28
CPC分类号： G06F19/12 , G01N33/5008 , G01N2500/10 , G06F19/18 , G06F19/28 , G06F19/704
摘要： The invention provides a computer readable medium or media, having: (a) a first data structure relating a plurality of reactants to a plurality of reactions from a first cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (b) a second data structure relating a plurality of reactants to a plurality of reactions from a second cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (c) a third data structure relating a plurality of intra-system reactants to a plurality of intra-system reactions between said first and second cells, each of said intra-system reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (d) a constraint set for said plurality of reactions for said first, second and third data structures, and (e) commands for determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said first and second data structures, wherein said at least one flux distribution is predictive of a physiological function of said first and second cells. The first, second and third data structures also can include a plurality of data structures. Additionally provided is a method for predicting a physiological function of a multicellular organism. The method includes: (a) providing a first data structure relating a plurality of reactants to a plurality of reactions from a first cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (b) providing a second data structure relating a plurality of reactants to a plurality of reactions from a second cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (c) providing a third data structure relating a plurality of intra-system reactants to a plurality of intra-system reactions between said first and second cells, each of said intra-system reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (d) providing a constraint set for said plurality of reactions for said first, second and third data structures; (e) providing an objective function, and (f) determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said first and second data structures, wherein said at least one flux distribution is predictive of a physiological function of said first and second cells.

3. 发明授权

US08697421B2 Methods and organisms for utilizing synthesis gas or other gaseous carbon sources and methanol 有权
标题翻译：利用合成气或其他气态碳源和甲醇的方法和生物
公开(公告)号：US08697421B2
公开(公告)日：2014-04-15
申请号：US13615168
申请日：2012-09-13
申请人： Mark J. Burk , Christophe H. Schilling , Anthony P. Burgard , John D. Trawick
发明人： Mark J. Burk , Christophe H. Schilling , Anthony P. Burgard , John D. Trawick
IPC分类号： C12N1/20 , C12N1/00 , C12P11/00 , C12P7/26 , C12P5/02 , C12P19/32 , C07H21/04
CPC分类号： C12P7/18 , C12N9/0008 , C12N9/0036 , C12N9/1007 , C12N9/93 , C12N15/70 , C12P19/32 , Y02E50/343
摘要： The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, CO2 and/or H2 to acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or CO2 and H2 to acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.
摘要翻译：本发明提供具有乙酰-CoA途径的非天然存在的微生物生物体，以及利用合成气或合成气和甲醇的能力。在一个实施方案中，本发明提供非天然存在的微生物，其包含一种或多种外源蛋白质，赋予微生物将CO，CO 2和/或H 2转化为乙酰辅酶A（乙酰辅酶A），甲基四氢叶酸（甲基 -THF）或其它所需产物，其中微生物缺乏在不存在一种或多种外源蛋白的情况下将CO或CO 2和H 2转化为乙酰辅酶A或甲基-THF的能力。本发明另外提供了生产乙酰辅酶A的方法，例如通过培养产生乙酰辅酶A的微生物，其中微生物生物体表达至少一种编码乙酰辅酶A途径酶或蛋白质的外源核酸，其量足够在条件下和足够的时间内产生乙酰辅酶A产生乙酰辅酶A。

4. 发明授权

US08455683B2 Methods for the synthesis of olefins and derivatives 有权
标题翻译：合成烯烃和衍生物的方法
公开(公告)号：US08455683B2
公开(公告)日：2013-06-04
申请号：US13219423
申请日：2011-08-26
申请人： Mark J. Burk , Priti Pharkya , Stephen J. Van Dien , Anthony P. Burgard , Christophe H. Schilling
发明人： Mark J. Burk , Priti Pharkya , Stephen J. Van Dien , Anthony P. Burgard , Christophe H. Schilling
IPC分类号： C07C57/04 , C12P7/40
CPC分类号： C07C51/353 , C07C51/38 , C07C57/04 , C07C67/08 , C07C67/32 , C07C67/333 , C12P7/40 , C12P7/46 , C12P7/62 , Y02P20/125 , C07C69/60 , C07C69/54
摘要： The invention provides a method of producing acrylic acid. The method includes contacting fumaric acid with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylic acid per mole of fumaric acid. Also provided is an acrylate ester. The method includes contacting fumarate diester with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylate ester per mole of fumarate diester. An integrated process for process for producing acrylic acid or acrylate ester is provided which couples bioproduction of fumaric acid with metathesis transformation. An acrylic acid and an acrylate ester production also is provided.
摘要翻译：本发明提供了制备丙烯酸的方法。该方法包括在交叉复分解转化催化剂存在下使富马酸与足够量的乙烯接触，以产生约2摩尔丙烯酸/摩尔富马酸。还提供了丙烯酸酯。该方法包括在交叉复分解转化催化剂存在下使富马酸二酯与足够量的乙烯接触，以产生每摩尔富马酸二酯约2摩尔丙烯酸酯。提供了用于生产丙烯酸或丙烯酸酯的方法的综合方法，其将富马酸的生物生产与易位转化相结合。还提供丙烯酸和丙烯酸酯生产。

5. 发明申请

US20130071883A1 METHODS AND ORGANISMS FOR UTILIZING SYNTHESIS GAS OR OTHER GASEOUS CARBON SOURCES AND METHANOL 有权
标题翻译：使用合成气或其他气态碳源和甲醇的方法和有机体
公开(公告)号：US20130071883A1
公开(公告)日：2013-03-21
申请号：US13615168
申请日：2012-09-13
申请人： Mark J. BURK , Christophe H. SCHILLING , Anthony P. BURGARD , John D. TRAWICK
发明人： Mark J. BURK , Christophe H. SCHILLING , Anthony P. BURGARD , John D. TRAWICK
IPC分类号： C12N1/21 , C12N1/19 , C12P19/32 , C12N1/15
CPC分类号： C12P7/18 , C12N9/0008 , C12N9/0036 , C12N9/1007 , C12N9/93 , C12N15/70 , C12P19/32 , Y02E50/343
摘要： The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, CO2 and/or H2 to acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or CO2 and H2 to acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to
摘要翻译：本发明提供具有乙酰-CoA途径的非天然存在的微生物生物体，以及利用合成气或合成气和甲醇的能力。在一个实施方案中，本发明提供非天然存在的微生物，其包含一种或多种外源蛋白质，赋予微生物将CO，CO 2和/或H 2转化为乙酰辅酶A（乙酰辅酶A），甲基四氢叶酸（甲基 -THF）或其它所需产物，其中微生物缺乏在不存在一种或多种外源蛋白的情况下将CO或CO 2和H 2转化为乙酰辅酶A或甲基-THF的能力。本发明另外提供了生产乙酰辅酶A的方法，例如通过培养产生乙酰辅酶A的微生物，其中微生物生物体表达至少一种编码乙酰辅酶A途径酶或蛋白质的外源核酸，其量足够在条件下和足够的时间内产生乙酰辅酶A

6. 发明授权

US08301430B2 Systems and methods for constructing genomic-based phenotypic models 有权
标题翻译：用于构建基因组型表型模型的系统和方法
公开(公告)号：US08301430B2
公开(公告)日：2012-10-30
申请号：US12947814
申请日：2010-11-16
申请人： Christophe H. Schilling
发明人： Christophe H. Schilling
IPC分类号： G06G7/58
CPC分类号： G06F19/12
摘要： The invention provides a computer implemented process for constructing a scalable output network model of a bioparticle. The process includes computer implemented steps of: (a) accessing a database of network gene components including an annotated network set of open reading frames (ORFs) of a bioparticle genome; (b) forming a data structure associating the network gene components with network reaction components, the data structure establishing a data set specifying a network model of connectivity and flow of the network reaction components, and (c) transforming the data set into a mathematical description of reactant fluxes defining the network model of connectivity and flow, wherein the mathematical description defines a scalable output network model of a bioparticle.
摘要翻译：本发明提供了一种用于构建生物颗粒的可伸缩输出网络模型的计算机实现过程。该过程包括计算机实现的步骤：（a）访问网络基因组件的数据库，包括生物颗粒基因组的开放阅读框（ORF）的注释网络集合; （b）形成将网络基因组件与网络反应组件相关联的数据结构，建立指定网络反应组件的连通性和流量的网络模型的数据集的数据结构，以及（c）将数据集转换为数学描述反应物通量定义了连通性和流量的网络模型，其中数学描述定义了生物颗粒的可伸缩输出网络模型。

7. 发明授权

US08229673B2 Human metabolic models and methods 有权
标题翻译：人类代谢模型和方法
公开(公告)号：US08229673B2
公开(公告)日：2012-07-24
申请号：US10402854
申请日：2003-03-27
申请人： Bornhard O. Palsson , Imandokht Famili , Markus W. Covert , Christophe H. Schilling
发明人： Bornhard O. Palsson , Imandokht Famili , Markus W. Covert , Christophe H. Schilling
IPC分类号： G01N33/50 , G01N33/48
CPC分类号： G06F19/12 , G06F19/18 , G06F19/28
摘要： The invention provides in silico models for determining the physiological function of human cells, including human skeletal muscle cells. The models include a data structure relating a plurality of Homo sapiens reactants to a plurality of Homo sapiens reactions, a constraint set for the plurality of Homo sapiens reactions, and commands for determining a distribution of flux through the reactions that is predictive of a Homo sapiens physiological function. A model of the invention can further include a gene database containing information characterizing the associated gene or genes. A regulated Homo sapiens reaction can be represented in a model of the invention by including a variable constraint for the regulated reaction. The invention further provides methods for making an in silico Homo sapiens model and methods for determining a Homo sapiens physiological function using a model of the invention.
摘要翻译：本发明提供了用于确定人类细胞（包括人类骨骼肌细胞）的生理功能的计算机模型。这些模型包括将多个智人反应物与多个智人反应相关联的数据结构，针对多个智人反应的约束集，以及用于确定通过反应的通量分布的命令，该反应预测人生理功能。本发明的模型还可以包括含有表征相关基因或基因的信息的基因数据库。调节的智人反应可以通过包括调节反应的可变约束在本发明的模型中表示。本发明还提供了使用本发明的模型制备计算机智人模型和用于确定智人生理功能的方法。

8. 发明申请

US20120185226A1 MAMMALIAN CELL LINE MODELS AND RELATED METHODS 有权
标题翻译： MAMMALIAN细胞系模型及相关方法
公开(公告)号：US20120185226A1
公开(公告)日：2012-07-19
申请号：US13203470
申请日：2010-02-26
申请人： Imandohkt Famili , Christophe H. Schilling
发明人： Imandohkt Famili , Christophe H. Schilling
IPC分类号： G06G7/60
CPC分类号： G06F19/12 , G06F19/26
摘要： The invention provides models and methods useful for optimizing cell lines. The invention provides methods and computer readable medium or media containing such methods. Such a computer readable medium or media can comprise commands for carrying out a method of the invention. The methods of the invention can be utilized to model improved characteristics of a cell line, for example, improved product production, improved growth, improved culture characteristics, and the like.
摘要翻译：本发明提供了用于优化细胞系的模型和方法。本发明提供了包含这些方法的方法和计算机可读介质或介质。这样的计算机可读介质或介质可以包括用于执行本发明的方法的命令。本发明的方法可用于模拟细胞系的改进特征，例如，改进的产物生产，改善的生长，改善的培养特征等。

9. 发明授权

US07856317B2 Systems and methods for constructing genomic-based phenotypic models 有权
标题翻译：用于构建基因组型表型模型的系统和方法
公开(公告)号：US07856317B2
公开(公告)日：2010-12-21
申请号：US10173547
申请日：2002-06-14
申请人： Christophe H. Schilling
发明人： Christophe H. Schilling
IPC分类号： G01N33/48
CPC分类号： G06F19/12
摘要： The invention provides a computer implemented process for constructing a scalable output network model of a bioparticle. The process includes computer implemented steps of: (a) accessing a database of network gene components including an annotated network set of open reading frames (ORFs) of a bioparticle genome; (b) forming a data structure associating the network gene components with network reaction components, the data structure establishing a data set specifying a network model of connectivity and flow of the network reaction components, and (c) transforming the data set into a mathematical description of reactant fluxes defining the network model of connectivity and flow, wherein the mathematical description defines a scalable output network model of a bioparticle.
摘要翻译：本发明提供了一种用于构建生物颗粒的可伸缩输出网络模型的计算机实现过程。该过程包括计算机实现的步骤：（a）访问网络基因组件的数据库，包括生物颗粒基因组的开放阅读框（ORF）的注释网络集合; （b）形成将网络基因组件与网络反应组件相关联的数据结构，数据结构建立指定网络反应组件的连通性和流程的网络模型的数据集，以及（c）将数据集变换为数学描述反应物通量定义了连通性和流量的网络模型，其中数学描述定义了生物颗粒的可伸缩输出网络模型。

10. 发明申请

US20090023182A1 COMPLEMENTARY METABOLIZING ORGANISMS AND METHODS OF MAKING SAME 审中-公开
公开(公告)号：US20090023182A1
公开(公告)日：2009-01-22
申请号：US11779865
申请日：2007-07-18
申请人： Christophe H. Schilling
发明人： Christophe H. Schilling
IPC分类号： C12P39/00 , C12N1/00
CPC分类号： C12P39/00 , C12N1/22 , C12P5/007 , C12P7/18 , C12P7/42 , C12P7/46 , C12P23/00
摘要： The invention provides a non-naturally occurring set of microbial organisms. The set of organisms includes: at least a first constituent complementary metabolizing organism (CMO) exhibiting the ability to metabolize a first carbon substrate and having substantially impaired metabolic capacity for a second carbon substrate, and at least a second constituent complementary metabolizing organism (CMO) exhibiting the ability to metabolize the second carbon substrate and having substantially impaired metabolic capacity for the first carbon substrate, wherein a co-culture of the at least first and second CMOs exhibit simultaneous metabolism of a mixture having the first and second carbon substrates compared to either CMO alone. Simultaneous metabolism of a mixture having first and second carbon substrates can include an enhanced rate of metabolism of the first and second substrates compared to either CMO alone. Also provided is a bioprocess for producing a chemical compound. The bioprocess includes co-culturing a non-naturally occurring set of microbial organisms in a mixture having at least a first and a second carbon substrate under conditions sufficient for biosynthesis of a target chemical compound, the set of non-naturally occurring microbial organisms including: at least a first constituent complementary metabolizing organism (CMO) exhibiting the ability to metabolize the first carbon substrate and having substantially impaired metabolic capacity for the second carbon substrate, and at least a second constituent complementary metabolizing organism (CMO) exhibiting the ability to metabolize the second carbon substrate and having substantially impaired metabolic capacity for the first carbon substrate, wherein a co-culture of the at least first and second CMOs exhibit simultaneous metabolism of a mixture having the first and second carbon substrates compared to either CMO alone. Simultaneous metabolism of a mixture having first and second carbon substrates can include an enhanced rate of metabolism of the first and second substrates compared to either CMO alone.

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