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1. 发明授权

US08871489B2 Metabolic evolution of Escherichia coli strains that produce organic acids 有权
标题翻译：产生有机酸的大肠杆菌菌株的代谢进化
公开(公告)号：US08871489B2
公开(公告)日：2014-10-28
申请号：US13394176
申请日：2010-11-17
申请人： Tammy Grabar , Wei Gong , R. Rogers Yocum
发明人： Tammy Grabar , Wei Gong , R. Rogers Yocum
IPC分类号： C12N1/20 , C12N1/00 , C12N15/74 , C07H21/04 , C07K14/245 , C12P7/46 , C12P7/54 , C12P7/40
CPC分类号： C07K14/245 , C12P7/40 , C12P7/46 , C12P7/54
摘要： This invention relates to the metabolic evolution of a microbial organism previously optimized for producing an organic acid in commercially significant quantities under fermentative conditions using a hexose sugar as sole source of carbon in a minimal mineral medium. As a result of this metabolic evolution, the microbial organism acquires the ability to use pentose sugars derived from cellulosic materials for its growth while retaining the original growth kinetics, the rate of organic acid production and the ability to use hexose sugars as a source of carbon. This invention also discloses the genetic change in the microorganism that confers the ability to use both the hexose and pentose sugars simultaneously in the production of commercially significant quantities of organic acids.
摘要翻译：本发明涉及先前优化用于在发酵条件下以商业上显着的量生产有机酸的微生物生物的代谢进化，其中使用己糖作为最小矿物培养基中的唯一碳源。作为这种代谢进化的结果，微生物生物体获得使用来自纤维素材料的戊糖的生长能力，同时保持原始生长动力学，有机酸生产速率和使用己糖作为碳源的能力。本发明还公开了赋予在生产商业上大量有机酸中同时使用己糖和戊糖的能力的微生物中的遗传变化。

2. 发明授权

US09017976B2 Engineering microbes for efficient production of chemicals 有权
标题翻译：用于高效生产化学品的工程微生物
公开(公告)号：US09017976B2
公开(公告)日：2015-04-28
申请号：US13503999
申请日：2010-11-17
申请人： Wei Gong , Sudhanshu Dole , Tammy Grabar , Andrew Christopher Collard , Janice G. Pero , R. Rogers Yocum
发明人： Wei Gong , Sudhanshu Dole , Tammy Grabar , Andrew Christopher Collard , Janice G. Pero , R. Rogers Yocum
IPC分类号： B29C70/04 , C12N15/74 , C12N1/00 , A61B6/04 , B29L31/00
CPC分类号： A61B6/0442 , B29C70/04 , B29L2031/753 , C12N9/1205 , C12N9/88 , C12N15/52 , C12P7/40 , C12P7/46
摘要： This present invention relates to production of chemicals from microorganisms that have been genetically engineered and metabolically evolved. Improvements in chemical production have been established, and particular mutations that lead to those improvements have been identified. Specific examples are given in the identification of mutations that occurred during the metabolic evolution of a bacterial strain genetically engineered to produce succinic acid. This present invention also provides a method for evaluating the industrial applicability of mutations that were selected during the metabolic evolution for increased succinic acid production. This present invention further provides microorganisms engineered to have mutations that are selected during metabolic evolution and contribute to improved production of succinic acid, other organic acids and other chemicals of commercial interest.
摘要翻译：本发明涉及从遗传工程和代谢进化的微生物生产化学物质。已经建立了化学生产的改进，并确定了导致这些改进的特定突变。在鉴定在遗传工程化生产琥珀酸的细菌菌株的代谢进化期间发生的突变的具体实例。本发明还提供了用于评估在增加的琥珀酸生产的代谢进化期间选择的突变的工业适用性的方法。本发明进一步提供了工程改造成具有在代谢进化期间选择的突变的微生物，并有助于改善琥珀酸，其它有机酸和其它商业利益的化学品的生产。

3. 发明申请

US20120202259A1 METABOLIC EVOLUTION OF ESCHERICHIS COLI STRAINS THAT PRODUCE ORGANIC ACIDS 有权
标题翻译：生产有机酸的ESCHERICHIS COLI菌株的代谢演化
公开(公告)号：US20120202259A1
公开(公告)日：2012-08-09
申请号：US13394176
申请日：2010-11-17
申请人： Tammy Grabar , Wei Gong , R. Rogers Yocum
发明人： Tammy Grabar , Wei Gong , R. Rogers Yocum
IPC分类号： C12P7/40 , C12N1/21
CPC分类号： C07K14/245 , C12P7/40 , C12P7/46 , C12P7/54
摘要： This invention relates to the metabolic evolution of a microbial organism previously optimized for producing an organic acid in commercially significant quantities under fermentative conditions using a hexose sugar as sole source of carbon in a minimal mineral medium. As a result of this metabolic evolution, the microbial organism acquires the ability to use pentose sugars derived from cellulosic materials for its growth while retaining the original growth kinetics, the rate of organic acid production and the ability to use hexose sugars as a source of carbon. This invention also discloses the genetic change in the microorganism that confers the ability to use both the hexose and pentose sugars simultaneously in the production of commercially significant quantities of organic acids.
摘要翻译：本发明涉及先前优化用于在发酵条件下以商业上显着的量生产有机酸的微生物生物的代谢进化，其中使用己糖作为最小矿物培养基中的唯一碳源。作为这种代谢进化的结果，微生物生物体获得使用来自纤维素材料的戊糖的生长能力，同时保持原始生长动力学，有机酸生产速率和使用己糖作为碳源的能力。本发明还公开了赋予在生产商业上大量有机酸中同时使用己糖和戊糖的能力的微生物中的遗传变化。

4. 发明申请

US20120220000A1 ENGINEERING MICROBES FOR EFFICIENT PRODUCTION OF CHEMICALS 有权
标题翻译：工程微生物高效生产化学品
公开(公告)号：US20120220000A1
公开(公告)日：2012-08-30
申请号：US13503999
申请日：2010-11-17
申请人： Wei Gong , Sudhanshu Dole , Tammy Grabar , Andrew Chirstopher Collard , Janice G. Pero , R. Rogers Yocum
发明人： Wei Gong , Sudhanshu Dole , Tammy Grabar , Andrew Chirstopher Collard , Janice G. Pero , R. Rogers Yocum
IPC分类号： C12P7/46 , C12N15/74 , C12N1/00
CPC分类号： A61B6/0442 , B29C70/04 , B29L2031/753 , C12N9/1205 , C12N9/88 , C12N15/52 , C12P7/40 , C12P7/46
摘要： This present invention relates to production of chemicals from microorganisms that have been genetically engineered and metabolically evolved. Improvements in chemical production have been established, and particular mutations that lead to those improvements have been identified. Specific examples are given in the identification of mutations that occurred during the metabolic evolution of a bacterial strain genetically engineered to produce succinic acid. This present invention also provides a method for evaluating the industrial applicability of mutations that were selected during the metabolic evolution for increased succinic acid production. This present invention further provides microorganisms engineered to have mutations that are selected during metabolic evolution and contribute to improved production of succinic acid, other organic acids and other chemicals of commercial interest.
摘要翻译：本发明涉及从遗传工程和代谢进化的微生物生产化学物质。已经建立了化学生产的改进，并确定了导致这些改进的特定突变。在鉴定在遗传工程化生产琥珀酸的细菌菌株的代谢进化期间发生的突变的具体实例。本发明还提供了用于评估在增加的琥珀酸生产的代谢进化期间选择的突变的工业适用性的方法。本发明进一步提供了工程改造成具有在代谢进化期间选择的突变的微生物，并有助于改善琥珀酸，其它有机酸和其它商业利益的化学品的生产。

5. 发明授权

US09845513B2 Method of producing succinic acid and other chemicals using sucrose-containing feedstock 有权
公开(公告)号：US09845513B2
公开(公告)日：2017-12-19
申请号：US13993150
申请日：2011-12-13
申请人： Sudhandshu Dole , R. Rogers Yocum , Theron Hermann , Xiaohui Yu
发明人： Sudhandshu Dole , R. Rogers Yocum , Theron Hermann , Xiaohui Yu
IPC分类号： C12P7/46 , C12R1/01 , C12N9/10 , C12N9/16 , C12P7/18 , C12P7/42
CPC分类号： C12R1/01 , C12N9/1051 , C12N9/16 , C12P7/18 , C12P7/42 , C12P7/46 , C12Y301/03024
摘要： This invention relates to the production of chemicals by fermentation with a microorganism in which the fermentation medium contains the sugar sucrose. As a specific example, succinic acid is produced from a sucrose-containing renewable feedstock through fermentation using a biocatalyst. Examples of such a biocatalyst include microorganisms that have been enhanced in their ability to utilize sucrose as a carbon and energy source. The biocatalysts of the present invention are derived from the genetic manipulation of parental strains that were originally constructed with the goal to produce one or more chemicals (for example succinic acid and/or a salt of succinic acid) at a commercial scale using feedstocks other than sucrose. The genetic manipulations of the present invention involve the introduction of exogenous genes involved in the transport and metabolism of sucrose into the parental strains. The genes involved in the transport and metabolism of sucrose can also be introduced into a microorganism prior to developing the organism to produce a particular chemical. The genes involved in the transport and metabolism of sucrose can also be used to augment or improve the sucrose transport and metabolism by strains already known to have some ability for sucrose utilization in biological fermentation.

6. 发明申请

US20090298137A1 MICROORGANISM AND PROCESS FOR THE PREPARATION OF L-METHIONINE 失效
标题翻译：用于制备L-甲硫氨酸的微生物和方法
公开(公告)号：US20090298137A1
公开(公告)日：2009-12-03
申请号：US12091948
申请日：2006-10-23
申请人： Oskar Zelder , Andreas Herold , Corinna Klopprogge , Hartwig Schröder , Stefan Haefner , Elmar Heinzle , Christoph Wittmann , Jens Kroemer , Janice G. Pero , R. Rogers Yocum , Thomas A. Patterson , Mark Williams , Theron Herman
发明人： Oskar Zelder , Andreas Herold , Corinna Klopprogge , Hartwig Schröder , Stefan Haefner , Elmar Heinzle , Christoph Wittmann , Jens Kroemer , Janice G. Pero , R. Rogers Yocum , Thomas A. Patterson , Mark Williams , Theron Herman
IPC分类号： C12P13/12 , C12N1/21
CPC分类号： C12P13/12 , A23K10/16 , A23K20/142 , A23K40/10 , C12N15/52
摘要： The present invention relates to microorganisms and processes for the efficient preparation of L-amino acids such as L-methionine. In particular, the present invention relates to microorganisms and processes in which the formation and/or accumulation of homolanthionine in the methionine pathway is reduced and/or prevented.
摘要翻译：本发明涉及用于有效制备L-氨基酸如L-甲硫氨酸的微生物和方法。特别地，本发明涉及微生物和其中甲硫氨酸途径中高山ion素的形成和/或积累减少和/或预防的方法。

7. 发明授权

US07291489B2 Microorganisms and processes for enhanced production of pantothenate 有权
标题翻译：用于增加泛酸盐生产的微生物和方法
公开(公告)号：US07291489B2
公开(公告)日：2007-11-06
申请号：US10614333
申请日：2003-07-03
申请人： R. Rogers Yocum , Thomas A. Patterson , Janice G. Pero , Theron Hermann
发明人： R. Rogers Yocum , Thomas A. Patterson , Janice G. Pero , Theron Hermann
IPC分类号： C12P13/04 , C12N9/00 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： C12N15/52 , C12P13/02
摘要： The present invention features improved methods for the enhanced production of pantoate and pantothenate utilizing microorganisms having modified pantothenate biosynthetic enzyme activities and having modified methylenetetrahydrofolate (MTF) biosynthetic enzyme activities. In particular, the invention features methods for enhancing production of desired products by increasing levels of a key intermediate, ketopantoate, by increasing enzymes or substrates that contribute directly or indirectly to its synthesis. Recombinant microorganisms and conditions for culturing same are also are featured. Also featured are compositions produced by such microorganisms.
摘要翻译：本发明的特征在于利用具有改良的泛酸生物合成酶活性并具有改性的亚甲基四氢叶酸（MTF）生物合成酶活性的微生物增强生产泛酸盐和泛酸盐的改进方法。特别地，本发明的特征在于通过增加对其合成直接或间接有贡献的酶或底物来增加关键中间体酮托品酸的水平来增强所需产物的产生的方法。还具有重组微生物和培养条件。还有这些微生物产生的组合物。

8. 发明授权

US08399214B2 Use of dimethyl disulfide for methionine production in microoraganisms 有权
标题翻译：用二甲基二硫化物在微生物激素中生产甲硫氨酸
公开(公告)号：US08399214B2
公开(公告)日：2013-03-19
申请号：US11988971
申请日：2006-07-18
申请人： Oskar Zelder , Stefan Haefner , Andrea Herold , Corinna Klopprogge , Hartwig Schroder , R. Rogers Yocum , Mark K. Williams
发明人： Oskar Zelder , Stefan Haefner , Andrea Herold , Corinna Klopprogge , Hartwig Schroder , R. Rogers Yocum , Mark K. Williams
IPC分类号： C12P1/00
CPC分类号： C12P13/12
摘要： The present invention features improved processes and organisms for the production of methionine. The invention demonstrates that a ΔmetF organism or a ΔmetE AmetH organism, for example, mutants of C. glutamicum or E. coli, can use a methyl capped sulfide source, e.g., dimethyl disulfide (DMDS), as a source of both sulfur and a methyl group, bypassing the need for MetH/MetE and MetF activity and the need to reduce sulfate, for the synthesis of methionine. Also described in this patent are data implicating MetY (also called MetZ) as an enzyme that incorporates a methyl capped sulfide source, e.g., DMDS, into methionine. A ΔmetF ΔmetB strain of C. glutamicum can use a methyl capped sulfide source, e.g., DMDS, as a source of both sulfide and a methyl group. Furthermore, methionine production by engineered prototrophic organisms that overproduce O-acetyl-homoserine was improved by the addition of a methyl capped sulfide source, e.g., DMDS.
摘要翻译：本发明的特征在于用于生产甲硫氨酸的改进方法和生物体。本发明证明，一种有机蛋白（MetF）生物体或一种具有谷氨酸棒状杆菌或大肠杆菌的突变体的MetE生物体可以使用例如二甲基二硫醚（DMDS）的甲基封端硫化物源作为硫和甲基，绕过MetH / MetE和MetF活性的需要，需要还原硫酸盐，用于合成甲硫氨酸。该专利中还描述的是涉及MetY（也称为MetZ）作为将甲基封端的硫化物源例如DMDS掺入甲硫氨酸的酶的数据。 A＆Dgr; metF＆Dgr;谷氨酸棒杆菌的metB菌株可以使用甲基封端的硫化物源，例如DMDS，作为硫化物和甲基的来源。此外，通过加入甲基封端的硫化物源（例如DMDS），改善过量产生O-乙酰高丝氨酸的工程化原养殖生物体的甲硫氨酸生产。

9. 发明申请

US20120225461A1 ORGANIC ACID PRODUCTION IN MICROORGANISMS BY COMBINED REDUCTIVE AND OXIDATIVE TRICABOXYLIC ACID CYLCE PATHWAYS 有权
标题翻译：通过组合还原和氧化三羧酸的循环途径在微生物中有机酸生产
公开(公告)号：US20120225461A1
公开(公告)日：2012-09-06
申请号：US13508095
申请日：2010-11-18
申请人： Sudhanshu Dole , R. Rogers Yocum
发明人： Sudhanshu Dole , R. Rogers Yocum
IPC分类号： C12P7/46 , C12N1/21
CPC分类号： C12N15/52 , C12N9/1025 , C12N9/1205 , C12N9/88 , C12P7/46
摘要： This invention relates to succinic acid production from renewable feedstock using microbial biocatalysts genetically modified to produce succinic acid in commercially significant quantities. More specifically, this invention relates to the genetic manipulations in the pathway of carbon from renewable feedstock to succinic acid.
摘要翻译：本发明涉及使用经遗传修饰以生产商业上显着量的琥珀酸的微生物生物催化剂从可再生原料生产琥珀酸。更具体地，本发明涉及从可再生原料到琥珀酸的碳通路中的遗传操作。

10. 发明授权

US08232081B2 Methods and microorganisms for production of panto-compounds 有权
标题翻译：泛化合物生产方法和微生物
公开(公告)号：US08232081B2
公开(公告)日：2012-07-31
申请号：US10984449
申请日：2004-11-08
申请人： R. Rogers Yocum , Thomas A. Patterson , Theron Hermann , Janice G. Pero
发明人： R. Rogers Yocum , Thomas A. Patterson , Theron Hermann , Janice G. Pero
IPC分类号： C12P13/04 , C12P13/02 , C12P7/42 , C12P7/18
CPC分类号： C12P17/04 , C12N15/52 , C12P13/02
摘要： The present invention features methods of producing panto-compounds (e.g., pantothenate) using microorganisms in which the pantothenate biosynthetic pathway and/or the isoleucine-valine biosynthetic pathway and/or the coenzymeA biosynthetic pathway has been manipulated. Methods featuring ketopantoate reductase overexpressing microorganisms as well as aspartate α-decarboxylase overexpressing microorganisms are provided. Methods of producing panto-compounds in a precursor-independent manner and in high yield are described. Recombinant microorganisms, vectors, isolated nucleic acid molecules, genes and gene products useful in practicing the above methodologies are also provided. The present invention also features a previously unidentified microbial pantothenate kinase gene, coaX, as well as methods of producing panto-compounds utilizing microorganisms having modified pantothenate kinase activity. Recombinant microorganisms, vectors, isolated coaX nucleic acid molecules and purified CoaX proteins are featured. Also featured are methods for identifying pantothenate kinase modulators utilizing the recombinant microorganisms and/or purified CoaX proteins of the present invention.
摘要翻译：本发明的特征在于使用其中泛酸生物合成途径和/或异亮氨酸 - 缬氨酸生物合成途径和/或辅酶A生物合成途径已经被操纵的微生物来生产泛化合物（例如泛酸盐）的方法。提供了酮过氧还原酶过表达微生物以及天冬氨酸α-脱羧酶过表达微生物的方法。描述了以前体非依赖性方式和高产率生产泛化合物的方法。还提供了用于实践上述方法的重组微生物，载体，分离的核酸分子，基因和基因产物。本发明还具有以前未鉴定的微生物泛酸激酶基因coaX，以及利用具有改良的泛酸激酶活性的微生物产生泛化合物的方法。重组微生物，载体，分离的coaX核酸分子和纯化的CoaX蛋白。还特征在于利用本发明的重组微生物和/或纯化的CoaX蛋白鉴定泛酸激酶调节剂的方法。

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