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    METHANOL DEHYDROGENASE FUSION PROTEINS
    152.
    发明公开
    METHANOL DEHYDROGENASE FUSION PROTEINS 审中-公开

    公开(公告)号：US20230265397A1

    公开(公告)日：2023-08-24

    申请号：US17943482

    申请日：2022-09-13

    Applicant: Genomatica, Inc.

    Inventor： Nelson R. Barton ,  Jingyi Li ,  Joseph R. Warner ,  Priti Pharkya

    IPC: C12N9/04 ,  C12N9/88 ,  C12N9/90 ,  C12N15/52 ,  C12N9/10 ,  C12P7/24

    CPC classification number: C12N9/0006 ,  C12N9/88 ,  C12N9/90 ,  C12Y401/02043 ,  C12Y503/01027 ,  C12N15/52 ,  C12N9/1029 ,  C12P7/24 ,  C12Y101/02007 ,  C12Y203/01085 ,  C12Y401/02013 ,  C07K2319/00

    Abstract: Described herein are fusion proteins including methanol dehydrogenase (MeDH) and at least one other polypeptide such as 3-hexulose-6-phosphate dehydrogenase (HPS) or 6-phospho-3-hexuloisomerase (PHI), such as DHAS synthase or fructose-6-Phosphate aldolase or such as DHA synthase or DHA kinase. In a localized manner, the fusion protein can promote the conversion of methanol to formaldehyde and then to a ketose phosphate such as hexulose 6-phosphate or then to DHA and G3P. When expressed in cells, the fusion proteins can promote methanol uptake and rapid conversion to the ketose phosphate or to the DHA and D3P, which in turn can be used in a pathway for the production of a desired bioproduct. Beneficially, the rapid conversion to the ketose phosphate or to the DHA and G3P can avoid the undesirable accumulation of formaldehyde in the cell. Also described are engineered cells expressing the fusion protein, 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.

    ALCOHOL DEHYDROGENASE VARIANTS
    154.
    发明公开
    ALCOHOL DEHYDROGENASE VARIANTS 审中-公开

    公开(公告)号：US20230159902A1

    公开(公告)日：2023-05-25

    申请号：US17861036

    申请日：2022-07-08

    Applicant: Genomatica, Inc.

    Inventor： Stefan ANDRAE ,  Michael Patrick KUCHINSKAS ,  Jingyi LI ,  Harish NAGARAJAN ,  Priti PHARKYA

    IPC: C12N9/04 ,  C12P7/24 ,  C12P7/18

    CPC classification number: C12N9/0006 ,  C12P7/24 ,  C12Y101/01244 ,  C12P7/18 ,  Y02P20/10 ,  C12Y101/01001

    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.

    Microorganisms for producing 1,4-butanediol and methods related thereto
    156.
    发明授权
    Microorganisms for producing 1,4-butanediol and methods related thereto 有权

    公开(公告)号：US11572564B2

    公开(公告)日：2023-02-07

    申请号：US15018736

    申请日：2016-02-08

    Applicant: Genomatica, Inc.

    Inventor： Wei Niu

    IPC: C12N15/52 ,  C12N9/02 ,  C12P7/16 ,  C12P7/18 ,  C12P7/42

    Abstract: The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO), 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway comprising at least one exogenous nucleic acid encoding a BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway enzyme expressed in a sufficient amount to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine.

    ALDEHYDE DEHYDROGENASE VARIANTS AND METHODS OF USE
    159.
    发明申请
    ALDEHYDE DEHYDROGENASE VARIANTS AND METHODS OF USE 有权

    公开(公告)号：US20220325254A1

    公开(公告)日：2022-10-13

    申请号：US17697504

    申请日：2022-03-17

    Applicant: Genomatica, Inc.

    Inventor： Kevin Hoff ,  Cara Ann Tracewell ,  Kui Chan ,  Amit Shah ,  Joseph Warner ,  Michael Noble

    IPC: C12N9/02

    Abstract: The invention provides polypeptides and encoding nucleic acids of aldehyde dehydrogenase variants. The invention also provides cells expressing aldehyde dehydrogenase variants. The invention further provides methods for producing 3-hydroxybutyraldehyde (3-HBal) and/or 1,3-butanediol (1,3-BDO), or an ester or amide thereof, comprising culturing cells expressing an aldehyde dehydrogenase variant or using lysates of such cells. The invention additional provides methods for producing 4-hydroxybutyraldehyde (4-HBal) and/or 1,4-butanediol (1,4-BDO), or an ester or amide thereof, comprising culturing cells expressing an aldehyde dehydrogenase variant or using lysates of such cells.

    OLIVETOLIC ACID CYCLASE VARIANTS AND METHODS FOR THEIR USE
    160.
    发明申请
    OLIVETOLIC ACID CYCLASE VARIANTS AND METHODS FOR THEIR USE 有权

    公开(公告)号：US20220315969A1

    公开(公告)日：2022-10-06

    申请号：US17616842

    申请日：2020-06-05

    Applicant: Genomatica Inc.

    Inventor： Michael Angus Noble ,  Russell Scott Komor

    IPC: C12P17/06 ,  C12N1/20 ,  C12N15/70 ,  C12N15/52 ,  C12P7/42

    Abstract: Described herein are olivetolic acid cyclases (OAC) including non-natural variants capable of forming a 2,4-dihydroxy-6-alkylbenzoic acid from a 3,5,7-trioxoacyl-CoA or a 3,5,7-trioxocarboxylate substrate. In some examples, the non-natural OAC is capable of forming a 2,4-dihydroxy-6-alkylbenzoic acid from a 3,5,7-trioxoacyl-CoA or a 3,5,7-trioxocarboxylate substrate at a greater rate. In some examples, the non-natural OAC has a higher affinity for a 3,5,7-trioxoacyl-CoA or a 3,5,7-trioxocarboxylate substrate, as compared to the wild type OAC. The non-natural OAC can be used with olivetol synthase (OLS) to form the 2,4-dihydroxy-6-alkylbenzoic acid from malonyl-CoA and acyl-CoA through to a 3,5,7-trioxoacyl-CoAintermediate. The non-natural OAC (and OLS) can be expressed in an engineered cell having a pathway to form cannabinoids, which include CBGA, its analogs and derivatives. CBGA can be used for the preparation of cannabigerol (CBG), which can be used in therapeutic compositions.

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