GB2579940B - Engineered benzylisoquinoline alkaloid epimerases and methods of producing benzylisoquinoline alkaloids - Google Patents
Engineered benzylisoquinoline alkaloid epimerases and methods of producing benzylisoquinoline alkaloids Download PDFInfo
- Publication number
- GB2579940B GB2579940B GB2002867.6A GB202002867A GB2579940B GB 2579940 B GB2579940 B GB 2579940B GB 202002867 A GB202002867 A GB 202002867A GB 2579940 B GB2579940 B GB 2579940B
- Authority
- GB
- United Kingdom
- Prior art keywords
- benzylisoquinoline
- epimerases
- engineered
- methods
- producing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 229930015408 benzyl-isoquinoline alkaloid Natural products 0.000 title 2
- 150000005516 benzylisoquinolines Chemical class 0.000 title 2
- 102000004879 Racemases and epimerases Human genes 0.000 title 1
- 108090001066 Racemases and epimerases Proteins 0.000 title 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/90—Isomerases (5.)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0014—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on the CH-NH2 group of donors (1.4)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0026—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on CH-NH groups of donors (1.5)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/10—Nitrogen as only ring hetero atom
- C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y105/00—Oxidoreductases acting on the CH-NH group of donors (1.5)
- C12Y105/01—Oxidoreductases acting on the CH-NH group of donors (1.5) with NAD+ or NADP+ as acceptor (1.5.1)
- C12Y105/01027—1,2-Dehydroreticulinium reductase (NADPH) (1.5.1.27)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/19—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14) with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water (1.14.19)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y501/00—Racemaces and epimerases (5.1)
- C12Y501/01—Racemaces and epimerases (5.1) acting on amino acids and derivatives (5.1.1)
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762541038P | 2017-08-03 | 2017-08-03 | |
| PCT/US2018/045222 WO2019028390A1 (en) | 2017-08-03 | 2018-08-03 | ALKALOID BENZYLISOQUINOLEIN GENETICALLY MODIFIED EPIMERASES AND METHODS FOR PRODUCING BENZYLISOQUINOLINE ALKALOIDS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB202002867D0 GB202002867D0 (en) | 2020-04-15 |
| GB2579940A GB2579940A (en) | 2020-07-08 |
| GB2579940B true GB2579940B (en) | 2022-11-30 |
Family
ID=65233084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB2002867.6A Active GB2579940B (en) | 2017-08-03 | 2018-08-03 | Engineered benzylisoquinoline alkaloid epimerases and methods of producing benzylisoquinoline alkaloids |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US10544420B2 (https=) |
| JP (1) | JP7199417B2 (https=) |
| BR (1) | BR112020002050A2 (https=) |
| GB (1) | GB2579940B (https=) |
| IL (1) | IL272363A (https=) |
| WO (1) | WO2019028390A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3475426A4 (en) | 2016-06-27 | 2020-08-19 | Serturner Corp. | POLYNUCLEOTIDES AND POLYPEPTIDES USEFUL FOR THE MANUFACTURE OF ALKALOID COMPOUNDS |
| WO2019028390A1 (en) | 2017-08-03 | 2019-02-07 | Antheia, Inc. | ALKALOID BENZYLISOQUINOLEIN GENETICALLY MODIFIED EPIMERASES AND METHODS FOR PRODUCING BENZYLISOQUINOLINE ALKALOIDS |
| US20200325509A1 (en) * | 2017-09-08 | 2020-10-15 | Intrexon Corporation | Microorganisms and Methods in the Fermentation of Benzylisoquinoline Alkaloids |
| WO2019157383A2 (en) * | 2018-02-08 | 2019-08-15 | Antheia, Inc. | Methods of producing morphinan alkaloids and derivatives |
| WO2020198373A1 (en) * | 2019-03-26 | 2020-10-01 | Antheia, Inc. | Methods of improving production of morphinan alkaloids and derivatives |
| EP3988663A4 (en) * | 2019-06-24 | 2023-08-02 | Ishikawa Prefectural Public University Corporation | Production method of (r)-reticulin |
| CN110179859B (zh) * | 2019-06-27 | 2021-09-24 | 香港科技大学深圳研究院 | 防己提取物及防己诺林碱在制药中的应用 |
| US20230332195A1 (en) * | 2019-10-10 | 2023-10-19 | River Stone Biotech Aps | Genetically modified host cells producing benzylisoquinoline alkaloids |
| CN111592989B (zh) * | 2020-06-28 | 2021-09-17 | 曲靖师范学院 | 一种曲霉菌Aspergillus sp.G12及其发酵制备异紫堇定碱的方法 |
| AU2023376563A1 (en) | 2022-11-08 | 2025-05-01 | River Stone Biotech Aps | Genetically modified benzylisoquinoline alkaloid-producing host cells with modified efflux transporter gene expression |
| CN116463310B (zh) * | 2022-11-11 | 2024-08-20 | 浙江中医药大学 | 一种粉防己4’-氧甲基转移酶4’-omt及应用 |
Citations (1)
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|---|---|---|---|---|
| WO2016183023A1 (en) * | 2015-05-08 | 2016-11-17 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of producing epimerases and benzylisoquinoline alkaloids |
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-
2018
- 2018-08-03 WO PCT/US2018/045222 patent/WO2019028390A1/en not_active Ceased
- 2018-08-03 GB GB2002867.6A patent/GB2579940B/en active Active
- 2018-08-03 JP JP2020505492A patent/JP7199417B2/ja active Active
- 2018-08-03 BR BR112020002050-8A patent/BR112020002050A2/pt unknown
- 2018-10-01 US US16/149,025 patent/US10544420B2/en active Active
-
2019
- 2019-08-14 US US16/541,078 patent/US11427827B2/en active Active
-
2020
- 2020-01-30 IL IL272363A patent/IL272363A/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016183023A1 (en) * | 2015-05-08 | 2016-11-17 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of producing epimerases and benzylisoquinoline alkaloids |
| US20180163241A1 (en) * | 2015-05-08 | 2018-06-14 | The Board Of Trustees Of The Leland Stanford Junior University | Methods of producing epimerases and benzylisoquinoline alkaloids |
Non-Patent Citations (5)
| Title |
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| FARROW, SC et al., "Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy", Nature Chemical Biology, (20150900), vol. 11, no. 9, pages 728 - 732, ; page 728, 2nd column, 2nd paragraph, page 729, 1st column, 1st paragraph. * |
| GIRVAN, HM et al., "Applications of microbial cytochrome P450 enzymes in biotechnology and synthetic biology", Current Opinion in Chemical Biology, (20160400), vol. 31, pages 136 - 145, page 139, 2nd column, 1st paragraph DOI: 10.1016/j.cbpa.2016.02.018 * * |
| KEENAN, C et al., "Uncovering the role of hydrophobic residues in Cytochrome P450-Cytochrome P450 reductase interactions", Biochemistry, (20110517), vol. 50, no. 19, pages 3957 - 3967, ; abstract; DOI: 10.1021/bi1020748 * * |
| ZELASKO, S et al., "Optimizations to achieve high-level expression of cytochrome P450 proteins using Escherichia coli expression systems", Protein Expression and Purification, (20131100), vol. 92, no. 1, pages 77 - 87, Table 1; DOI: 10.1 016/j.pep.2013.07 .017 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2020529848A (ja) | 2020-10-15 |
| US20200157551A1 (en) | 2020-05-21 |
| BR112020002050A2 (pt) | 2020-09-08 |
| GB2579940A (en) | 2020-07-08 |
| US20190078100A1 (en) | 2019-03-14 |
| US10544420B2 (en) | 2020-01-28 |
| WO2019028390A1 (en) | 2019-02-07 |
| JP7199417B2 (ja) | 2023-01-05 |
| IL272363A (en) | 2020-03-31 |
| US11427827B2 (en) | 2022-08-30 |
| GB202002867D0 (en) | 2020-04-15 |
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