JPWO2020050273A1 - グルタチオンの製造方法 - Google Patents
グルタチオンの製造方法 Download PDFInfo
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- JPWO2020050273A1 JPWO2020050273A1 JP2020541239A JP2020541239A JPWO2020050273A1 JP WO2020050273 A1 JPWO2020050273 A1 JP WO2020050273A1 JP 2020541239 A JP2020541239 A JP 2020541239A JP 2020541239 A JP2020541239 A JP 2020541239A JP WO2020050273 A1 JPWO2020050273 A1 JP WO2020050273A1
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- amino acid
- glutathione
- yeast
- acid sequence
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- C—CHEMISTRY; METALLURGY
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- 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
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- 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
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01148181A (ja) * | 1987-12-07 | 1989-06-09 | Jgc Corp | グルタチオンの菌体内蓄積法 |
JP2004180509A (ja) * | 2002-11-29 | 2004-07-02 | Kanegafuchi Chem Ind Co Ltd | グルタチオン高含有酵母およびそれを培養して得られる食品又は医薬品、又は化粧品用素材 |
WO2011118807A1 (fr) * | 2010-03-26 | 2011-09-29 | アサヒビール株式会社 | Procédé de culture de levure |
JP2013169168A (ja) * | 2012-02-20 | 2013-09-02 | Kaneka Corp | グルタチオンの製造方法 |
JP2014064472A (ja) * | 2012-09-24 | 2014-04-17 | Kaneka Corp | グルタチオンの製造方法 |
KR20150071264A (ko) * | 2013-12-18 | 2015-06-26 | (주)푸른들이엠사료 | 글루타치온을 고발현하는 신규 균주 및 글루타치온 대량 생산 방법 |
WO2016140349A1 (fr) * | 2015-03-04 | 2016-09-09 | 株式会社カネカ | Procédé de production de glutathion |
-
2019
- 2019-09-03 CN CN201980054912.8A patent/CN112639117A/zh active Pending
- 2019-09-03 JP JP2020541239A patent/JPWO2020050273A1/ja active Pending
- 2019-09-03 WO PCT/JP2019/034630 patent/WO2020050273A1/fr active Application Filing
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01148181A (ja) * | 1987-12-07 | 1989-06-09 | Jgc Corp | グルタチオンの菌体内蓄積法 |
JP2004180509A (ja) * | 2002-11-29 | 2004-07-02 | Kanegafuchi Chem Ind Co Ltd | グルタチオン高含有酵母およびそれを培養して得られる食品又は医薬品、又は化粧品用素材 |
WO2011118807A1 (fr) * | 2010-03-26 | 2011-09-29 | アサヒビール株式会社 | Procédé de culture de levure |
JP2013169168A (ja) * | 2012-02-20 | 2013-09-02 | Kaneka Corp | グルタチオンの製造方法 |
JP2014064472A (ja) * | 2012-09-24 | 2014-04-17 | Kaneka Corp | グルタチオンの製造方法 |
KR20150071264A (ko) * | 2013-12-18 | 2015-06-26 | (주)푸른들이엠사료 | 글루타치온을 고발현하는 신규 균주 및 글루타치온 대량 생산 방법 |
WO2016140349A1 (fr) * | 2015-03-04 | 2016-09-09 | 株式会社カネカ | Procédé de production de glutathion |
Non-Patent Citations (1)
Title |
---|
CURRENT TRENDS IN BIOTECHNOLOGY AND PHARMACY, vol. 6, no. 2, JPN6019044612, 2012, pages 241 - 254, ISSN: 0005190598 * |
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