公开(公告)号：US20140030779A1

公开(公告)日：2014-01-30

申请号：US13908907

申请日：2013-06-03

Applicant: Priti PHARKYA ,  Anthony P. BURGARD ,  Stephen J. VAN DIEN ,  Robin E. OSTERHOUT ,  Mark J. BURK ,  John D. TRAWICK ,  Michael P. KUCHINSKAS ,  Brian STEER

Inventor： Priti PHARKYA ,  Anthony P. BURGARD ,  Stephen J. VAN DIEN ,  Robin E. OSTERHOUT ,  Mark J. BURK ,  John D. TRAWICK ,  Michael P. KUCHINSKAS ,  Brian STEER

IPC: C12P7/42 ,  C12N15/63

CPC classification number: C12N1/20 ,  C07C31/207 ,  C07C59/01 ,  C08G18/284 ,  C08G18/3206 ,  C08G63/06 ,  C08G63/16 ,  C08G63/181 ,  C08G69/02 ,  C12N9/18 ,  C12N15/52 ,  C12N15/63 ,  C12P7/18 ,  C12P7/42 ,  C12Y301/01 ,  Y02P20/52

Abstract: The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate pathway and being capable of producing 4-hydroxybutyrate, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyrate or related products using the microbial organisms.

Abstract translation: 本发明提供具有4-羟基丁酸途径并且能够产生4-羟基丁酸酯的非天然存在的微生物生物，其中微生物生物体包含一种或多种遗传修饰。 本发明另外提供了使用微生物生物制备4-羟基丁酸酯或相关产品的方法。

公开(公告)号：US08617862B2

公开(公告)日：2013-12-31

申请号：US13527455

申请日：2012-06-19

Applicant: Anthony P. Burgard ,  Robin E. Osterhout ,  Jun Sun ,  Priti Pharkya ,  Mark J. Burk

Inventor： Anthony P. Burgard ,  Robin E. Osterhout ,  Jun Sun ,  Priti Pharkya ,  Mark J. Burk

IPC: C12P5/02 ,  C12P5/00 ,  C12P1/04

CPC classification number: C12P5/026 ,  C12N1/20 ,  C12N9/0004 ,  C12N9/1007

Abstract: The invention provides non-naturally occurring microbial organisms having a propylene pathway. The invention additionally provides methods of using such organisms to produce propylene.

Abstract translation: 本发明提供具有丙烯途径的非天然存在的微生物。 本发明另外提供了使用这些生物来生产丙烯的方法。

公开(公告)号：US08455683B2

公开(公告)日：2013-06-04

申请号：US13219423

申请日：2011-08-26

Applicant: Mark J. Burk ,  Priti Pharkya ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Christophe H. Schilling

Inventor： Mark J. Burk ,  Priti Pharkya ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Christophe H. Schilling

IPC: C07C57/04 ,  C12P7/40

CPC classification number: C07C51/353 ,  C07C51/38 ,  C07C57/04 ,  C07C67/08 ,  C07C67/32 ,  C07C67/333 ,  C12P7/40 ,  C12P7/46 ,  C12P7/62 ,  Y02P20/125 ,  C07C69/60 ,  C07C69/54

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20130071883A1

公开(公告)日：2013-03-21

申请号：US13615168

申请日：2012-09-13

Applicant: Mark J. BURK ,  Christophe H. SCHILLING ,  Anthony P. BURGARD ,  John D. TRAWICK

Inventor： Mark J. BURK ,  Christophe H. SCHILLING ,  Anthony P. BURGARD ,  John D. TRAWICK

IPC: C12N1/21 ,  C12N1/19 ,  C12P19/32 ,  C12N1/15

CPC classification number: C12P7/18 ,  C12N9/0008 ,  C12N9/0036 ,  C12N9/1007 ,  C12N9/93 ,  C12N15/70 ,  C12P19/32 ,  Y02E50/343

Abstract: 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

Abstract translation: 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

公开(公告)号：US08377680B2

公开(公告)日：2013-02-19

申请号：US12776365

申请日：2010-05-07

Applicant: Mark J. Burk ,  Anthony P. Burgard ,  Robin E. Osterhout ,  Priti Pharkya

Inventor： Mark J. Burk ,  Anthony P. Burgard ,  Robin E. Osterhout ,  Priti Pharkya

IPC: C12N1/20 ,  C12N1/00 ,  C12N15/70 ,  C12P7/42 ,  C12P13/00 ,  C12P17/10 ,  C07H21/04

CPC classification number: C12P17/10 ,  C12N1/38 ,  C12N15/52 ,  C12P7/40 ,  C12P7/44 ,  C12P13/001 ,  C12P13/005 ,  C12P13/02 ,  C12P17/12

Abstract: The invention provides a non-naturally occurring microbial organism having a 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in the respective 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The invention additionally provides a method for producing 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid. The method can include culturing a 6-aminocaproic acid, caprolactam or hexametheylenediamine producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway enzyme in a sufficient amount to produce the respective product, under conditions and for a sufficient period of time to produce 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid.

Abstract translation: 本发明提供了具有6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸途径的非天然存在的微生物生物。 微生物生物体含有至少一种编码各自的6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸途径中的酶的外源核酸。 本发明另外提供了制备6-氨基己酸，己内酰胺，己二胺或乙酰丙酸的方法。 该方法可以包括培养6-氨基己酸，己内酰胺或六亚甲基二胺生产微生物，其中微生物生物体表达至少一种编码6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸途径酶的外源核酸，其量足以产生 各自的产物在条件下和足够的时间内产生6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸。

公开(公告)号：US08357520B2

公开(公告)日：2013-01-22

申请号：US13348564

申请日：2012-01-11

Applicant: Mark J. Burk ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Wei Niu

Inventor： Mark J. Burk ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Wei Niu

IPC: C12P7/18 ,  C12N1/21

CPC classification number: C12N15/52 ,  B01D3/002 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/88 ,  C12N9/93 ,  C12N15/70 ,  C12N15/81 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12Y101/01061 ,  C12Y102/01076 ,  C12Y401/01071 ,  C12Y602/01004 ,  Y02P20/52

Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or α-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided are methods for the production of 4-HB and BDO.

公开(公告)号：US08301430B2

公开(公告)日：2012-10-30

申请号：US12947814

申请日：2010-11-16

Applicant: Christophe H. Schilling

Inventor： Christophe H. Schilling

IPC: G06G7/58

CPC classification number: G06F19/12

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20120208249A1

公开(公告)日：2012-08-16

申请号：US13371278

申请日：2012-02-10

Applicant: John D. Trawick ,  Mark J. Burk ,  Anthony P. Burgard

Inventor： John D. Trawick ,  Mark J. Burk ,  Anthony P. Burgard

IPC: C12P7/18 ,  C12N1/21

CPC classification number: C12P7/18 ,  C12N9/0006 ,  C12N9/10 ,  C12N9/1029 ,  C12N9/88 ,  C12N15/52 ,  C12P7/04 ,  C12P7/42

Abstract: A non-naturally occurring microbial organism having an isopropanol, 4-hydroxybutryate, or 1,4-butanediol pathway includes at least one exogenous nucleic acid encoding an isopropanol, 4-hydroxybutryate, or 1,4-butanediol pathway enzyme expressed in a sufficient amount to produce isopropanol, 4-hydroxybutryate, or 1,4-butanediol. The aforementioned organisms are cultured to produce isopropanol, 4-hydroxybutryate, or 1,4-butanediol.

Abstract translation: 具有异丙醇，4-羟基丁酸酯或1,4-丁二醇途径的非天然存在的微生物包括至少一种编码以足够量表达的异丙醇，4-羟基丁酸酯或1,4-丁二醇途径酶的外源核酸 产生异丙醇，4-羟基丁酸酯或1,4-丁二醇。 培养上述生物体以产生异丙醇，4-羟基丁酸酯或1,4-丁二醇。

公开(公告)号：US08236539B2

公开(公告)日：2012-08-07

申请号：US13011788

申请日：2011-01-21

Applicant: Anthony P. Burgard ,  Robin E. Osterhout ,  Jun Sun ,  Priti Pharkya

Inventor： Anthony P. Burgard ,  Robin E. Osterhout ,  Jun Sun ,  Priti Pharkya

IPC: C12N9/00 ,  C12N1/20

Abstract: A non-naturally occurring microbial organism includes a microbial organism having a reductive TCA or Wood-Ljungdahl pathway in which at least one exogenous nucleic acid encoding these pathway enzymes is expressed in a sufficient amount to enhance carbon flux through acetyl-CoA. A method for enhancing carbon flux through acetyl-CoA includes culturing theses non-naturally occurring microbial organisms under conditions and for a sufficient period of time to produce a product having acetyl-CoA as a building block. Another non-naturally occurring microbial organism includes at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance the availability of reducing equivalents in the presence of carbon monoxide or hydrogen, thereby increasing the yield of redox-limited products via carbohydrate-based carbon feedstock. A method for enhancing the availability of reducing equivalents in the presence of carbon monoxide or hydrogen includes culturing this organism for a sufficient period of time to produce a product.

公开(公告)号：US08229673B2

公开(公告)日：2012-07-24

申请号：US10402854

申请日：2003-03-27

Applicant: Bornhard O. Palsson ,  Imandokht Famili ,  Markus W. Covert ,  Christophe H. Schilling

Inventor： Bornhard O. Palsson ,  Imandokht Famili ,  Markus W. Covert ,  Christophe H. Schilling

IPC: G01N33/50 ,  G01N33/48

CPC classification number: G06F19/12 ,  G06F19/18 ,  G06F19/28

Abstract: 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.

Abstract translation: 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。