公开(公告)号：US20240124904A1

公开(公告)日：2024-04-18

申请号：US18453987

申请日：2023-08-22

Applicant: Genomatica, Inc.

Inventor： Anthony P. Burgard ,  Robin E. Osterhout ,  Stephen J. Van Dien ,  Priti Pharkya ,  Tae Hoon Yang ,  Jungik Choi

IPC: C12P7/18 ,  C07K14/245 ,  C12N1/20 ,  C12N9/00 ,  C12N9/02 ,  C12N9/12 ,  C12N9/16 ,  C12N9/52 ,  C12N9/88 ,  C12N15/52 ,  C12P7/42

CPC classification number: C12P7/18 ,  C07K14/245 ,  C12N1/20 ,  C12N9/0036 ,  C12N9/0057 ,  C12N9/1205 ,  C12N9/16 ,  C12N9/52 ,  C12N9/88 ,  C12N9/93 ,  C12N15/52 ,  C12P7/42 ,  C12Y106/01002 ,  C12Y110/03 ,  C12Y207/0104 ,  C12Y301/00 ,  C12Y301/02 ,  C12Y301/02002 ,  C12Y304/21092 ,  C12Y401/01031 ,  C12Y401/01032

Abstract: −The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.

公开(公告)号：US10597684B2

公开(公告)日：2020-03-24

申请号：US15108259

申请日：2014-12-23

Applicant: Genomatica, Inc.

Inventor： Anthony P. Burgard ,  Robin E. Osterhout ,  Stephen J. Van Dien ,  Priti Pharkya ,  Tae Hoon Yang ,  Jungik Choi

IPC: C12P7/18 ,  C12P7/42 ,  C07K14/245 ,  C12N9/00 ,  C12N1/20 ,  C12N9/88 ,  C12N9/52 ,  C12N15/52 ,  C12N9/16 ,  C12N9/02 ,  C12N9/12

Abstract: The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.

公开(公告)号：US20230287435A1

公开(公告)日：2023-09-14

申请号：US17772990

申请日：2020-10-28

Applicant: Genomatica, Inc.

Inventor： Harish Nagarajan ,  Gionata Scalcinati ,  Tae Hoon Yang

IPC: C12N15/52 ,  C12P7/18

CPC classification number: C12N15/52 ,  C12P7/18 ,  C12Y202/01006 ,  C12Y104/99001 ,  C12Y501/01001 ,  C12Y102/01003 ,  C12Y602/01001 ,  C12Y203/03001

Abstract: The present disclosure provides microbial organisms having decreased production of unwanted by-products (e.g, pyruvate-, CO2—, TCA-derived by-products; acetate; ethanol; and/or, alanine) to enhance carbon flux through acetyl-CoA, which can increase production of acetyl-CoA derived compounds (e.g, 1,3-BDO, MMA, and (3R)-hydroxybutyl (3R)-hydroxybutyrate, or any other acetyl-CoA derived compounds), and products made from any of these compounds. Also provided are one or more exogenous nucleic acids encoding enzymes that can decrease production of unwanted by-products (e.g, aldehyde dehydrogenase, acetyl-CoA synthase, amino acid dehydrogenase, alanine racemase, and/or citrate synthase), and/or one or more gene attenuations occurring in genes (e.g., acetolactate synthase) that result in decreased production of unwanted by-products. Various combinations of the exogenous nucleic acids and gene deletions are also provided in the present disclosure. Methods of making and using the same, including methods for culturing cells, and for the production of the various products are also provided.

公开(公告)号：US20220177895A1

公开(公告)日：2022-06-09

申请号：US17255352

申请日：2019-06-26

Applicant: Genomatica, Inc.

Inventor： Harish Nagarajan ,  Tae Hoon Yang ,  Ali Khodayari

IPC: C12N15/52 ,  C12N9/02 ,  C12N9/16 ,  C12N9/88 ,  C12N9/90 ,  C12P13/00 ,  C12P5/00 ,  C12P5/02 ,  C12P7/16 ,  C12P7/18 ,  C12P7/24 ,  C12P7/42 ,  C12P7/46 ,  C12P7/6409

Abstract: Described herein are engineered cells including ones having synthetic methylotrophy which include an NADH-dependent enzyme capable of converting G3P to 3PG (e.g., B. methanolicus gapN) and/or fructose-1,6-bisphosphatase, along with hexulose-6-phosphate synthase, 6-phospho-3-hexuloisomerase, a phosphoketolase, or a combination thereof. Engineered cells of the disclosure beneficially maintain adequate pool sizes of phosphorylated C3 and/or C4 compounds, and/or provide increased levels of NADPH. As such, the modifications allow for the generation of C6 compounds from C1 (e.g., a methanol feedstod) and C5 compounds, the regeneration of C5 compounds from C6 compounds by carbon rearrangement, and an improved balance between regeneration of C5 compounds and lower glycolysis. In turn, this allows the engineered microorganism to generate sufficient quantities of metabolic precursors (e.g., acetyl-CoA) which can be used in a bioproduct pathway, and the engineered cells can include further modifications to those pathway enzymes allowing for production of a desired bioproduct.

公开(公告)号：US20210147883A1

公开(公告)日：2021-05-20

申请号：US16785510

申请日：2020-02-07

Applicant: Genomatica, Inc.

Inventor： Anthony P. Burgard ,  Robin E. Osterhout ,  Stephen J. Van Dien ,  Priti Pharkya ,  Tae Hoon Yang ,  Jungik Choi

IPC: C12P7/18 ,  C12N9/02 ,  C12N9/12 ,  C12N9/16 ,  C12N15/52 ,  C12N1/20 ,  C12N9/00 ,  C07K14/245 ,  C12P7/42 ,  C12N9/52 ,  C12N9/88

Abstract: The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.

公开(公告)号：US12234463B2

公开(公告)日：2025-02-25

申请号：US17255352

申请日：2019-06-26

Applicant: Genomatica, Inc.

Inventor： Harish Nagarajan ,  Tae Hoon Yang ,  Ali Khodayari

IPC: C12N9/16 ,  C12N9/02 ,  C12N9/88 ,  C12N9/90 ,  C12N15/52 ,  C12P5/00 ,  C12P5/02 ,  C12P7/16 ,  C12P7/18 ,  C12P7/24 ,  C12P7/42 ,  C12P7/46 ,  C12P7/6409 ,  C12P13/00

Abstract: Described herein are engineered cells including ones having synthetic methylotrophy which include an NADH-dependent enzyme capable of converting G3P to 3PG (e.g., B. methanolicus gapN) and/or fructose-1,6-bisphosphatase, along with hexulose-6-phosphate synthase, 6-phospho-3-hexuloisomerase, a phosphoketolase, or a combination thereof. Engineered cells of the disclosure beneficially maintain adequate pool sizes of phosphorylated C3 and/or C4 compounds, and/or provide increased levels of NADPH. As such, the modifications allow for the generation of C6 compounds from C1 (e.g., a methanol feedstod) and C5 compounds, the regeneration of C5 compounds from C6 compounds by carbon rearrangement, and an improved balance between regeneration of C5 compounds and lower glycolysis. In turn, this allows the engineered microorganism to generate sufficient quantities of metabolic precursors (e.g., acetyl-CoA) which can be used in a bioproduct pathway, and the engineered cells can include further modifications to those pathway enzymes allowing for production of a desired bioproduct.

公开(公告)号：US20220403420A1

公开(公告)日：2022-12-22

申请号：US17770233

申请日：2020-10-22

Applicant: Genomatica, Inc.

Inventor： Harish Nagarajan ,  Gionata Scalcinati ,  Tae Hoon Yang

IPC: C12P7/18 ,  C12N9/02 ,  C12N9/12 ,  C12N9/04

Abstract: The present disclosure provides microbial organisms having increased availability of co-factors, such as NADPH, for increasing production of various products, including 1,3-BDO, MMA, (3R)-hydroxybutyl (3R)-hydroxybutyrate, amino acids, 3HB-CoA, adipate, caprolactam, 6-ACA, HMD A, or MAA, and products made from any of these. Also provided are one or more exogenous nucleic acids encoding an enzyme expressed in a sufficient amount to increase availability of NADPH, where the exogenous nucleic acid includes one or more of ATP-NADH kinase, pntAB, nadK, and gapN. Also provided are one or more gene attenuations occurring in genes, such as NDH-2, that result in an increased ratio of NADPH to NADH. Various combinations of the exogenous nucleic acids and gene deletions are also provided in the present disclosure. The present disclosure also provides methods of making and using the same, including methods for culturing cells, and for the production of the various products.