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    ALCOHOL DEHYDROGENASE VARIANTS
    61.
    发明申请
    ALCOHOL DEHYDROGENASE VARIANTS 审中-公开
    酒精脱水变异

    公开(公告)号：US20160237410A1

    公开(公告)日：2016-08-18

    申请号：US15027169

    申请日：2014-10-03

    Applicant: GENOMATICA, INC.

    Inventor： Stefan Andrae ,  Michael Patrick Kuchinskas ,  Jingyi Li ,  Harish Nagarajan ,  Priti Pharkya

    IPC: C12N9/04 ,  C12P7/24

    Abstract: Described herein are non-natural NAD+-dependent alcohol dehydrogenases (ADHs) capable of at least two fold greater conversion of methanol or ethanol to formaldehyde or acetaldehyde, respectively, as compared to its unmodified counterpart. Nucleic acids encoding the non-natural alcohol dehydrogenases, as well as expression constructs including the nucleic acids, and engineered cells comprising the nucleic acids or expression constructs are described. Also described are engineered cells expressing a non-natural NAD+-dependent alcohol dehydrogenase, optionally include one or more additional metabolic pathway transgene(s), methanol metabolic pathway genes, target product pathway genes, cell culture compositions including the cells, methods for promoting production of the target product or intermediate thereof from the cells, compositions including the target product or intermediate, and products made from the target product or intermediate.

    Abstract translation: 本文描述了与其未修饰的对应物相比，能够分别甲醇或乙醇转化为甲醛或乙醛的至少两倍的非天然NAD +依赖性醇脱氢酶（ADH）。 描述了编码非天然醇脱氢酶的核酸，以及包含核酸的表达构建体和包含核酸或表达构建体的工程化细胞。 还描述了表达非天然NAD +依赖性醇脱氢酶的工程细胞，任选地包括一种或多种另外的代谢途径转基因，甲醇代谢途径基因，靶产物途径基因，包括细胞的细胞培养组合物，用于促进生产的方法 的靶产物或其中间体，包括靶产物或中间体的组合物，以及由目标产物或中间体制成的产品。

    MULTICELLULAR METABOLIC MODELS AND METHODS
    62.
    发明申请
    MULTICELLULAR METABOLIC MODELS AND METHODS 审中-公开

    公开(公告)号：US20150302141A1

    公开(公告)日：2015-10-22

    申请号：US14572615

    申请日：2014-12-16

    Applicant: Genomatica, Inc.

    Inventor： Imandokht FAMILI ,  Christophe H. SCHILLING

    IPC: G06F19/12 ,  G06F19/00 ,  G01N33/50 ,  G06F19/28

    CPC classification number: G16B5/00 ,  G01N33/5008 ,  G01N2500/10 ,  G16B20/00 ,  G16B50/00 ,  G16C20/30

    Abstract: 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.

    PRODUCTION METHOD FOR 1,4-BUTANEDIOL
    65.
    发明申请
    PRODUCTION METHOD FOR 1,4-BUTANEDIOL 审中-公开
    1,4-丁二醇的生产方法

    公开(公告)号：US20150087038A1

    公开(公告)日：2015-03-26

    申请号：US14560714

    申请日：2014-12-04

    Applicant: MITSUBISHI CHEMICAL CORPORATION ,  GENOMATICA, INC.

    Inventor： Masaru UTSUNOMIYA ,  Yusuke IZAWA ,  Norikazu KONISHI ,  Kota TANAKA ,  Shinichiro MATSUZONO ,  Takayuki SUZUKI ,  Michael JAPS ,  Mark BURK ,  Warren CLARK

    IPC: C07C29/84 ,  C12P7/18

    CPC classification number: C07C29/84 ,  B01D3/002 ,  B01D3/143 ,  C07C29/80 ,  C12P7/18 ,  C07C31/207

    Abstract: An object of the present invention is to provide high-quality 1,4BG capable of working out to a raw material of PBT with good color tone, by efficiently removing and refining impurities mixed when producing a biomass-derived 1,4BG on an industrial scale and the present invention relates to a production method of refined 1,4BG, where a crude 1,4BG-containing solution is obtained from refined raw material 1,4BG obtained by removing bacterial cells, salt contents and water from the fermentation culture medium, through a step of removing high-boiling-point components and/or low-boiling-point components by distillation and/or a step of converting an unsaturated compound to a hydride and the target product is obtained as a side stream in a further distillation step.

    Abstract translation: 本发明的目的是提供一种能够通过在工业规模生产生物质衍生的1,4BG时有效地除去和精制混合的杂质来提供具有良好色调的PBT原料的高质量的1,4BG 本发明涉及精制的1,4BG的制造方法，其中，通过从发酵培养基中除去细菌细胞，盐含量和水，通过从精制原料1,4BG获得粗制的含1,4BG的溶液，通过 通过蒸馏除去高沸点组分和/或低沸点组分的步骤和/或将不饱和化合物转化为氢化物的步骤，并在另外的蒸馏步骤中作为副产物获得目标产物。

    MICROORGANISMS AND PROCESSES FOR PRODUCING TEREPHTHALIC ACID AND ITS SALTS
    66.
    发明申请
    MICROORGANISMS AND PROCESSES FOR PRODUCING TEREPHTHALIC ACID AND ITS SALTS 审中-公开
    生产正辛酸及其盐的微生物和方法

    公开(公告)号：US20150080547A1

    公开(公告)日：2015-03-19

    申请号：US14373160

    申请日：2013-01-18

    Applicant: Genomatica, Inc.

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

    IPC: C12P7/44 ,  C12P7/62 ,  C08G63/183 ,  C12P7/40

    CPC classification number: C12P7/44 ,  C07C51/43 ,  C07F9/091 ,  C08G63/183 ,  C12N9/0004 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/1007 ,  C12N9/1022 ,  C12N9/1085 ,  C12N9/1205 ,  C12N9/88 ,  C12P7/24 ,  C12P7/40 ,  C12P7/62 ,  C12P9/00 ,  C07C63/26 ,  C07C63/04

    Abstract: The invention provides non-naturally occurring microbial organisms having a (2-hydroxy-3-methyl-4-oxobutoxy) phosphonate (2H3M40P) pathway, p-toluate pathway, and/or terephthalate pathway. The invention additionally provides methods of using such organisms to produce 2H3M40P, p-toluate or terephthalate. Also provided herein are processes for isolating bio-based aromatic carboxylic acid, in particular, p-toluic acid or terephthalic acid, from a culture medium, wherein the processes involve contacting the culture medium with sufficient carbon dioxide (C02) to lower the pH of the culture medium to produce a precipitate comprised of the aromatic carboxylic acid.

    Abstract translation: 本发明提供具有（2-羟基-3-甲基-4-氧代丁氧基）膦酸酯（2H3M40P）途径，对甲苯甲酸途径和/或对苯二酸酯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体来生产2H3M40P，对甲苯甲酸酯或对苯二甲酸酯的方法。 本文还提供了从培养基中分离生物基芳族羧酸，特别是对甲苯甲酸或对苯二甲酸的方法，其中所述方法包括使培养基与足够的二氧化碳（CO 2）接触以降低 该培养基产生由芳族羧酸组成的沉淀物。

    MICROORGANISMS AND METHODS FOR THE BIOSYNTHESIS OF AROMATICS, 2,4-PENTADIENOATE AND 1,3-BUTADIENE
    67.
    发明申请
    MICROORGANISMS AND METHODS FOR THE BIOSYNTHESIS OF AROMATICS, 2,4-PENTADIENOATE AND 1,3-BUTADIENE 审中-公开
    芳香族化合物的2,4-二戊二酸和1,3-丁二烯的生物合成的微生物和方法

    公开(公告)号：US20150064750A1

    公开(公告)日：2015-03-05

    申请号：US14226631

    申请日：2014-03-26

    Applicant: Genomatica, Inc.

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

    IPC: C12P7/62 ,  C12P5/02

    CPC classification number: C12P7/62 ,  C12N15/52 ,  C12P5/005 ,  C12P5/026 ,  C12P7/16 ,  C12P7/40 ,  C12P9/00 ,  Y02E50/10

    Abstract: The invention provides non-naturally occurring microbial organisms having a toluene, benzene, p-toluate, terephthalate, (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate, (2-hydroxy-4-oxobutoxy)phosphonate, benzoate, styrene, 2,4-pentadienoate, 3-butene-1ol or 1,3-butadiene pathway. The invention additionally provides methods of using such organisms to produce toluene, benzene, p-toluate, terephthalate, (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate, (2-hydroxy-4-oxobutoxy)phosphonate, benzoate, styrene, 2,4-pentadienoate, 3-butene-1ol or 1,3-butadiene.

    Abstract translation: 本发明提供了具有甲苯，苯，对甲苯甲酸酯，对苯二甲酸酯，（2-羟基-3-甲基-4-氧代丁氧基）膦酸酯，（2-羟基-4-氧代丁氧基）膦酸酯，苯甲酸酯，苯乙烯 ，2,4-戊二烯酸酯，3-丁烯-1醇或1,3-丁二烯途径。 本发明另外提供了使用这些生物体来生产甲苯，苯，对甲苯甲酸酯，对苯二甲酸酯，（2-羟基-3-甲基-4-氧代丁氧基）膦酸酯，（2-羟基-4-氧代丁氧基）膦酸酯，苯甲酸酯，苯乙烯 ，2,4-戊二烯酸酯，3-丁烯-1醇或1,3-丁二烯。

    Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors
    68.
    发明授权
    Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors 有权
    1,4-丁二醇及其前体的生物合成的组合物和方法

    公开(公告)号：US08969054B2

    公开(公告)日：2015-03-03

    申请号：US13717350

    申请日：2012-12-17

    Applicant: Genomatica, Inc.

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

    IPC: C12P7/18 ,  C12N1/21 ,  C12P7/42 ,  C12N9/04 ,  C12N9/02 ,  C12N9/88 ,  C12N9/00 ,  C12P7/52 ,  C12P17/04

    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.

    Abstract translation: 本发明提供了一种非天然存在的微生物生物催化剂，其包括具有4-羟基丁酸（4-HB）生物合成途径的微生物生物，其具有至少一种编码4-羟基丁酸脱氢酶的外源核酸，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸半醛 脱氢酶或α-酮戊二酸脱羧酶，其中外源核酸以足够的量表达以产生单体4-羟基丁酸（4-HB）。 还提供了非天然存在的微生物生物催化剂，其包括具有4-羟基丁酸（4-HB）和1,4-丁二醇（BDO）生物合成途径的微生物生物，该途径包括至少一种编码4-羟基丁酸脱氢酶的外源核酸 ，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸半醛脱氢酶，4-羟基丁酸酯：CoA转移酶，4-丁酸酯激酶，磷酸转移酶，α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶，其中外源核酸为 以足够的量表示产生1,4-丁二醇（BDO）。 另外提供了用于生产4-HB和BDO的方法。

    Semisynthetic routes to organic compounds
    70.
    发明授权
    Semisynthetic routes to organic compounds 有权

    公开(公告)号：US12188068B2

    公开(公告)日：2025-01-07

    申请号：US17229543

    申请日：2021-04-13

    Applicant: Genomatica, Inc.

    Inventor： Stephen B. Del Cardayre ,  Andreas W. Schirmer ,  Myong Ko ,  Haibo Wang

    IPC: C12P17/08 ,  C12P7/42 ,  C12P7/44 ,  C12P17/04

    Abstract: The present disclosure relates to chemo-enzymatic processes for the preparation of lactones (including, e.g., macrolactones, γ-lactones, and δ-lactones) and/or macrocyclic ketones, which are compounds of industrial value, for example, for use as fragrance ingredients. The chemo-enzymatic processes combine the in vivo microbial production of fatty acid derivatives and the subsequent ex vivo synthetic transformation of the fatty acid derivatives to provide the lactones and macrocyclic ketones.

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