WO2023136421A1 - Mutant chez escherichia ayant une productivité de l-histidine améliorée et procédé de production de l-histidine l'utilisant - Google Patents
Mutant chez escherichia ayant une productivité de l-histidine améliorée et procédé de production de l-histidine l'utilisant Download PDFInfo
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- WO2023136421A1 WO2023136421A1 PCT/KR2022/013162 KR2022013162W WO2023136421A1 WO 2023136421 A1 WO2023136421 A1 WO 2023136421A1 KR 2022013162 W KR2022013162 W KR 2022013162W WO 2023136421 A1 WO2023136421 A1 WO 2023136421A1
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- histidine
- escherichia
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- galp
- mutant
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/245—Escherichia (G)
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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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
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- 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
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
- C12P13/24—Proline; Hydroxyproline; Histidine
Definitions
- the present invention relates to a mutant strain of the genus Escherichia with improved L-histidine-producing ability and a method for producing L-histidine using the same.
- L-Histidine is an essential amino acid that is not synthesized in the human or animal body and must be supplied from the outside, and is generally produced by fermentation using microorganisms such as bacteria or yeast.
- microorganisms such as bacteria or yeast.
- a wild-type strain obtained in nature or a mutant strain modified to improve L-histidine-producing ability may be used.
- genetic recombination technology was applied to microorganisms such as Escherichia coli and Corynebacterium, which are widely used in the production of L-amino acids and other useful substances.
- Various recombinant strains or mutant strains and L-histidine production methods using the same are being developed.
- Korean Patent Registration Nos. 10-1904666 and 10-2004917 disclose a method of increasing histidine production by inducing genetic mutations in enzymes or transport proteins involved in the histidine biosynthetic pathway to enhance or weaken the activity of the corresponding protein. has been initiated. In addition, a method of adjusting the expression level of a substance acting on histidine production or optimizing the metabolic flow is also used.
- Patent Document 1 Korean Patent Registration No. 10-1904666
- Patent Document 2 Korea Patent Registration No. 10-2004917
- An object of the present invention is to provide a mutant strain of the genus Escherichia with improved L-histidine production ability.
- an object of the present invention is to provide a method for producing L-histidine using the mutant strain.
- the present inventors found that the gene galP encoding the galactose: H+ companion transporter was selected for smooth carbon source supply in the L-histidine biosynthesis process.
- the present invention was completed by confirming that the production of L-histidine increased in the case of overexpression.
- One aspect of the present invention provides an Escherichia genus mutant with improved L-histidine production ability by enhancing the activity of the galactose:H+ companion transporter.
- the “galactose:H+ symporter” used in the present invention is a type of membrane protein that transports sugars such as galactose and glucose into cells, and is also called galactose permease.
- “enhanced activity” means that the expression of a gene encoding a protein such as a target enzyme, transcription factor, transport protein, etc. is newly introduced or increased, and the expression level is increased compared to the wild-type strain or the strain before modification. .
- the enhancement of this activity is when the activity of the protein itself is increased compared to the activity of the protein originally possessed by the microorganism through nucleotide substitution, insertion, deletion, or a combination encoding the gene, and increased expression or translation of the gene encoding it etc., if the overall protein activity level in the cell is higher than that of the wild-type strain or the strain before modification, a combination thereof is also included.
- the enhancement of the activity of the galactose:H+ companion transporter is performed by introducing a gene encoding the galactose:H+ companion transporter, or by introducing a site specific promoter of a gene encoding the galactose:H+ companion transporter. It may be the cause of the enemy mutation.
- promoter refers to a specific region of DNA that regulates the transcription of a gene, including a binding site for RNA polymerase that initiates mRNA transcription of a gene of interest, and is generally the starting point of transcription. It is located upstream based on .
- Prokaryotes in prokaryotes are defined as sites around the start of transcription where RNA polymerase binds, and are generally composed of two short nucleotide sequences separated by -10 and -35 base pairs forward from the start of transcription. .
- Promoter mutation in the present invention is improved to have higher activity than wild-type promoter, mutation in the promoter region located upstream of the transcription start point, more specifically, mutation in part or all by insertion, substitution, deletion, or a combination thereof can increase the expression of genes located downstream.
- the galactose:H+ companion transporter may be derived from a strain of the genus Escherichia.
- the Escherichia genus strain is Escherichia coli ( Escherichia coli ), Escherichia Alberti ( Escherichia albertii ), Escherichia blattae ( Escherichia blattae ), Escherichia fergusonii ( Escherichia fergusonii ), Escheri Chia Hermanni ( Escherichia hermannii ) And Escherichia vulneris ( Escherichia vulneris ) It may be one or more species selected from the group consisting of, but is not limited thereto.
- the galactose:H+ companion transporter may be a mutation in which some or all of the genes derived from the strain of Escherichia are inserted, substituted, deleted, or a combination thereof.
- “Some” used in the present invention means not all of the amino acid sequence, base sequence or polynucleotide sequence, and may be 1 to 300, preferably 1 to 100, more preferably 1 to 50, It is not limited to this.
- the gene encoding the galactose:H+ companion transporter may be represented by the nucleotide sequence of SEQ ID NO: 1.
- the gene encoding the galactose:H+ companion transporter may be represented by the amino acid sequence of SEQ ID NO: 2.
- “Improved productivity” used in the present invention means that the productivity of L-histidine is increased compared to the parent strain.
- the parent strain refers to a wild-type or mutant strain subject to mutation, and includes a subject subject to direct mutation or transformed into a recombinant vector.
- the parent strain may be a wild-type strain of Escherichia genus or a strain of the genus Escherichia mutated from the wild-type strain.
- the parent strain is Escherichia coli ( Escherichia coli ), Escherichia Alberti ( Escherichia albertii ), Escherichia blattae ( Escherichia blattae ), Escherichia fergusonii ( Escherichia fergusonii ) , Escherichia Hermanni ( Escherichia hermannii ) and Escherichia vulneris ( Escherichia vulneris ) It may be one or more selected from the group consisting of.
- E. coli DS9H strain (KCTC18430P) was used as a parent strain.
- the mutant strain may be Escherichia coli, that is, Escherichia coli.
- a galP gene encoding a galactose:H+ companion transporter was introduced into E. coli to obtain a galP-introduced mutant strain.
- This mutant strain exhibits an increased L-histidine production ability compared to the parent strain due to improved glucose absorption ability by the introduction of galP, and in particular, L-histidine production compared to the parent strain is 5% or more, specifically 5 to 40% (preferably is increased by 10 to 30%) to produce 8 to 20 g of L-histidine per liter of the strain culture medium, preferably 8.5 to 15 g of L-histidine.
- the poxB gene may be derived from a strain of the genus Escherichia. More specifically, the poxB gene is Escherichia coli ( Escherichia coli ), Escherichia Alberti ( Escherichia albertii ), Escherichia blattae ( Escherichia blattae ), Escherichia fergusonii ( Escherichia fergusonii ), Escherichia Hermann It may be derived from one strain selected from the group consisting of Escherichia hermannii and Escherichia vulneris , but is not limited thereto.
- the poxB gene may be represented by the nucleotide sequence of SEQ ID NO: 3 or the amino acid sequence of SEQ ID NO: 4.
- a mutant strain of the genus Escherichia can be implemented through a recombinant vector containing a galP gene encoding a galactose:H+ companion transporter or a variant thereof in a parent strain.
- mutant refers to a mutant in which part or all of the galP gene encoding the galactose:H+ companion transporter involved in the biosynthesis of L-histidine is inserted, substituted, deleted, or a combination thereof.
- vector is an expression vector capable of expressing a target protein in a suitable host cell, and refers to a gene product containing essential regulatory elements operably linked to express a gene insert.
- operably linked means that a gene requiring expression and its regulatory sequence are functionally linked to each other to enable gene expression
- regulatory element refers to a promoter for performing transcription and regulating transcription. sequences encoding suitable mRNA ribosome binding sites, and sequences that control termination of transcription and translation.
- vectors include, but are not limited to, plasmid vectors, cosmid vectors, bacteriophage vectors, viral vectors, and the like.
- the “recombinant vector” used in the present invention can be replicated independently of the genome of the host cell or can be incorporated into the genome itself.
- the "suitable host cell” is capable of replicating the vector and may include an origin of replication, which is a specific nucleotide sequence at which replication is initiated.
- a suitable vector introduction technique is selected according to the host cell, and the desired gene can be expressed in the host cell.
- vector introduction can be performed by electroporation, heat-shock, calcium phosphate (CaPO4) precipitation, calcium chloride (CaCl2) precipitation, microinjection, polyethylene glycol (PEG) method, DEAE- It may be performed by a dextran method, a cationic liposome method, a lithium acetate-DMSO method, or a combination thereof.
- the transformed gene may be included without limitation, whether it is inserted into the chromosome of the host cell or located outside the chromosome, as long as it can be expressed in the host cell.
- the host cell includes a cell transfected, transformed, or infected with the recombinant vector or polynucleotide of the present invention in vivo or in vitro.
- a host cell containing the recombinant vector of the present invention is a recombinant host cell, recombinant cell or recombinant microorganism.
- the recombinant vector according to the present invention may include a selection marker.
- the selection marker is for selecting transformants (host cells) transformed with the vector in a medium treated with the selection marker. Since only cells expressing the selectable marker can survive, selection of transformed cells is possible.
- Representative examples of the selectable marker include kanamycin, streptomycin, and chloramphenicol, but are not limited thereto.
- Genes inserted into the recombinant vector for transformation of the present invention may be substituted into a host cell such as a microorganism of the genus Escherichia by homologous recombination crossing.
- the host cell may be an Escherichia genus strain, for example, E. coli.
- another aspect of the present invention is a) culturing the Escherichia genus mutant in a medium; and b) recovering L-histidine from the mutant strain or a culture medium in which the mutant strain is cultured.
- the culture may be performed according to appropriate media and culture conditions known in the art, and those skilled in the art can easily adjust and use the media and culture conditions.
- the medium may be a liquid medium, but is not limited thereto.
- the culture method may include, for example, batch culture, continuous culture, fed-batch culture, or a combination culture thereof, but is not limited thereto.
- the medium must meet the requirements of a particular strain in an appropriate way, and can be appropriately modified by a person skilled in the art.
- Carbon sources that can be used include sugars and carbohydrates such as glucose, sucrose, lactose, fructose, maltose, starch and cellulose, oils and fats such as soybean oil, sunflower oil, castor oil, coconut oil, palmitic acid, stearic acid, These include fatty acids such as linoleic acid, alcohols such as glycerol and ethanol, and organic acids such as acetic acid. These materials may be used individually or as a mixture, but are not limited thereto.
- Nitrogen sources that can be used include peptone, yeast extract, broth, malt extract, corn steep liquor, soybean meal and urea or inorganic compounds such as ammonium sulfate, ammonium chloride, ammonium phosphate, ammonium carbonate and ammonium nitrate. Nitrogen sources may also be used individually or as a mixture, but are not limited thereto. Sources of phosphorus that may be used include, but are not limited to, potassium dihydrogen phosphate or dipotassium hydrogen phosphate or the corresponding sodium-containing salts.
- the culture medium may contain metal salts such as magnesium sulfate or iron sulfate necessary for growth, but is not limited thereto.
- essential growth substances such as amino acids and vitamins may be included. Precursors suitable for the culture medium may also be used. The medium or individual components may be added in a batchwise or continuous manner by a method suitable for the culture medium during the culture process, but is not limited thereto.
- the pH of the culture medium can be adjusted by adding compounds such as ammonium hydroxide, potassium hydroxide, ammonia, phosphoric acid and sulfuric acid to the microbial culture medium in an appropriate manner during cultivation.
- the formation of bubbles can be suppressed by using an antifoaming agent such as a fatty acid polyglycol ester during cultivation.
- oxygen or oxygen-containing gas eg, air
- the temperature of the culture medium may be usually 20 ° C to 45 ° C, for example, 25 ° C to 40 ° C.
- the culturing period may be continued until useful substances are obtained in a desired yield, and may be, for example, 10 to 160 hours.
- the step of recovering L-histidine from the cultured mutant and the medium in which the mutant is cultured is L-histidine produced from the medium using a suitable method known in the art according to the culture method.
- a suitable method known in the art according to the culture method can be collected or retrieved.
- centrifugation, filtration, extraction, spraying, drying, evaporation, precipitation, crystallization, electrophoresis, fractionation (eg ammonium sulfate precipitation), chromatography (eg ion exchange, affinity, hydrophobicity and Size exclusion) may be used, but is not limited thereto.
- the culture medium in the step of recovering histidine, is centrifuged at low speed to remove biomass, and the obtained supernatant may be separated through ion exchange chromatography.
- the recovering L-histidine may include a process of purifying L-histidine.
- the mutant strain of the genus Escherichia according to the present invention can improve the production yield of L-histidine by increasing sugar availability by increasing or enhancing the expression of the gene encoding the galactose:H+ companion transporter.
- the galP gene was amplified by PCR from E. coli DS9H (KCTC18430P) genomic DNA using galP-F and galP-R primer pairs and pfu premix (bioneer). As PCR conditions, the total volume of the reaction was 50 ⁇ l and reacted at 95 ° C for 5 minutes, followed by a total of 30 times at 95 ° C for 30 seconds, 58 ° C for 30 seconds, and 72 ° C for 1 minute / kb, followed by 72 It was held for 5 minutes at °C and 10 minutes at 12 °C. Subsequently, PCR amplification was performed under the same conditions.
- Primer name Primer sequence (5'-3') sequence number galP-F ATATCCATGGATGCCTGACGCTAAAAAACAG 5 galP-R ATATAAGCTTTTAATCGTGAGCGCCTATTTCG 6 pTRC99A-CF ATATTCTGAAATGAGCTGTTGACAA 7 pTRC99A-CR TACTGCCGCCAGGCAAATTC 8
- the E. coli DS9H strain into which the galP gene was introduced was cultured at 37° C. on LB medium containing 10.0 g of tryptone, 10.0 g of NaCl, 5.0 g of yeast extract, and 100 mg/L of ampicillin in 1 L of distilled water.
- Antibiotics kanamycin and ampicillin were used as products of Sigma.
- DNA sequencing analysis was performed by requesting Macrogen Co., Ltd.
- a one-step inactivation method (Warner et al., PNAS, 6:6640-6645 (2000)) was used to introduce galP into the chromosome of E. coli DS9H strain (KCTC18430P).
- the down-stream of the pgi gene was selected as an introduction site in the chromosome of the corresponding gene for homologous recombination.
- PCR amplification using E was obtained.
- coli DS9H genomic DNA as a template and the Dpgi_HF-F and Dpgi_HF-R primer pairs, and the Dpgi_HR-F and Dpgi_HR-R primer pairs, respectively Through, the Dpgi_HF and Dpgi_HR fragments were amplified, respectively.
- a cassette fragment was obtained from the pKD13 plasmid through PCR amplification using a primer pair FRT(Dpgi_HF)-F and FRT(galP)-R.
- Trc-galP a Trc-galP fragment was obtained from the pTRC99A-galP plasmid of Example 1 through PCR amplification using galP+FRT-F and galP+Dpgi_HR-R primer pairs.
- the total volume of the reaction was 50 ⁇ l and reacted at 95 ° C for 5 minutes, followed by a total of 30 times at 95 ° C for 30 seconds, 58 ° C for 30 seconds, and 72 ° C for 1 minute / kb, followed by 72 It was held for 5 minutes at °C and 10 minutes at 12 °C.
- PCR amplification was performed under the same conditions.
- PCR was performed on the kanamycin-resistant cell lines using the Dpgi-CF and Dpgi-CR primer pairs to identify strains into which the kanamycin cassette was introduced.
- the antibiotic (kanamycin) resistance gene was removed from the strains for which the introduction was confirmed.
- whether the antibiotic was removed was confirmed by examining growth on LB plates without and with antibiotic (kanamycin) added, respectively. It was confirmed using the fact that the strains from which the antibiotic gene was removed grew on the LB plate medium, but did not grow on the LB plate medium to which the antibiotic (kanamycin, 50 mg/L) was added.
- the sequence was confirmed using the Dpgi-CF and Dpgi-CR primer pairs, and a galP-introduced mutant (DS9H-1) was obtained.
- Primer name Primer sequence (5'-3') sequence number Dpgi_HF-F GCAGGAATATCGTGATCAGGG 9 Dpgi_HF-R GCCAGCTGTTTACCCAGTTC 10 FRT(Dpgi_HF)-F GAACTGGGTAAACAGCTGGCGTGTAGGCTGGAGCTGCTTC 11 FRT(galP)-R ATCAATTCGCGCTAACTCACACATGAGAATTAATTCCGGGG 12 galP+FRT-F CCCGGAATTAATTCTCATGTGTGAGTTAGCGAATTGATCTG 13 galP+Dgpi_HR-R ACCTTGTAGGCCTGATAAGACTTAATCGTGAGCGCCTATTTCG 14 Dpgi_HR-F GTCTTATCAGGCCTACAGGTCG 15 Dpgi_HR-R CAAAAGCAATTAATCTGCGTAT 16 Dpgi-CF ATACCGGCAAAGCAATCACTG 17 Dpgi-CR AGTATACACAACTAAAGCATGCG 18
- a one-step inactivation method (Warner et al., PNAS, 6:6640-6645 (2000)) was used for galP introduction and poxB disruption into the chromosome of E. coli DS9H strain (KCTC18430P).
- E. coli DS9H genomic DNA was used as a template, and the poxB_HF-F and poxB_HF-R primer pairs and the poxB_HR-F and poxB_HR-R primer pairs were respectively used.
- the poxB_HF and poxB_HR fragments were amplified, respectively, through PCR amplification.
- Trc-galP a Trc-galP fragment was obtained from the pTRC99A-galP plasmid of Example 1 through PCR amplification using galP+FRT-F and galP+poxB_HR-R primer pairs. Using these four PCR fragments as templates, they were linked into one fragment by overlapping PCR using the poxB_HF-F and poxB_HR-R primer pairs. DNA fragments linked together were introduced into E. coli DS9H strain containing the pKD46 plasmid by electroporation (Tauch et al., FEMS Microbiology letters 123 (1994) 343-347).
- PCR was performed using the poxB-CF and poxB-CR primer pairs targeting the kanamycin-resistant cell lines, and galP-introduced strains were identified. Subsequently, in the same manner as in Example 2, a mutant strain (DS9H-2) in which galP was introduced and poxB was deleted was obtained.
- mutant DS9H-1 increased the production of L-histidine by about 10% and the rate of sugar consumption by about 5.6% compared to the parent strain by introducing the galP gene. It was confirmed that the L-histidine production increased by about 21% and the sugar consumption rate improved by about 3.8% compared to the strain.
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Abstract
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202280088644.3A CN118525095A (zh) | 2022-01-11 | 2022-09-02 | L-组氨酸生产能力得到提高的埃希菌属变异株及利用其的l-组氨酸的生产方法 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2022-0004001 | 2022-01-11 | ||
| KR1020220004001A KR20230108789A (ko) | 2022-01-11 | 2022-01-11 | L-히스티딘 생산능이 향상된 에스케리치아 속 변이주 및 이를 이용한 l-히스티딘의 생산 방법 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023136421A1 true WO2023136421A1 (fr) | 2023-07-20 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2022/013162 Ceased WO2023136421A1 (fr) | 2022-01-11 | 2022-09-02 | Mutant chez escherichia ayant une productivité de l-histidine améliorée et procédé de production de l-histidine l'utilisant |
Country Status (3)
| Country | Link |
|---|---|
| KR (2) | KR20230108789A (fr) |
| CN (1) | CN118525095A (fr) |
| WO (1) | WO2023136421A1 (fr) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040214294A1 (en) * | 2003-04-01 | 2004-10-28 | Mechthild Rieping | Process for the production of L-amino acids using strains of the enterobacteriaceae family |
| KR20040099299A (ko) * | 2002-03-07 | 2004-11-26 | 데구사 악티엔게젤샤프트 | 아미노산 생성 박테리아 및 l-아미노산의 제조 방법 |
| KR20150105600A (ko) * | 2014-02-12 | 2015-09-17 | 씨제이제일제당 (주) | L-쓰레오닌 생산능을 가지는 재조합 에스케리키아 속 미생물 및 이를 이용한 l-쓰레오닌의 생산방법 |
| WO2021126961A1 (fr) * | 2019-12-16 | 2021-06-24 | Ginkgo Bioworks, Inc. | Production améliorée d'histidine, de métabolites de la voie purine et d'adn plasmidique |
| KR20210136416A (ko) * | 2020-05-07 | 2021-11-17 | (주)에스티알바이오텍 | 뮤코닉산 전구체 생산용 미생물 및 이를 이용한 뮤코닉산 전구체 생산방법 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101904666B1 (ko) | 2017-08-02 | 2018-11-29 | 씨제이제일제당 (주) | Atp 포스포리보실기 전이효소 변이체 및 이를 이용한 l-히스티딘 생산방법 |
| KR102004917B1 (ko) | 2017-10-31 | 2019-07-30 | 광운대학교 산학협력단 | 애플리케이션 사용내역 정보에 기초하여 조명을 제어하는 장치 및 방법 |
-
2022
- 2022-01-11 KR KR1020220004001A patent/KR20230108789A/ko not_active Ceased
- 2022-09-02 WO PCT/KR2022/013162 patent/WO2023136421A1/fr not_active Ceased
- 2022-09-02 CN CN202280088644.3A patent/CN118525095A/zh active Pending
-
2024
- 2024-10-11 KR KR1020240138690A patent/KR20240153302A/ko active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20040099299A (ko) * | 2002-03-07 | 2004-11-26 | 데구사 악티엔게젤샤프트 | 아미노산 생성 박테리아 및 l-아미노산의 제조 방법 |
| US20040214294A1 (en) * | 2003-04-01 | 2004-10-28 | Mechthild Rieping | Process for the production of L-amino acids using strains of the enterobacteriaceae family |
| KR20150105600A (ko) * | 2014-02-12 | 2015-09-17 | 씨제이제일제당 (주) | L-쓰레오닌 생산능을 가지는 재조합 에스케리키아 속 미생물 및 이를 이용한 l-쓰레오닌의 생산방법 |
| WO2021126961A1 (fr) * | 2019-12-16 | 2021-06-24 | Ginkgo Bioworks, Inc. | Production améliorée d'histidine, de métabolites de la voie purine et d'adn plasmidique |
| KR20210136416A (ko) * | 2020-05-07 | 2021-11-17 | (주)에스티알바이오텍 | 뮤코닉산 전구체 생산용 미생물 및 이를 이용한 뮤코닉산 전구체 생산방법 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20230108789A (ko) | 2023-07-19 |
| CN118525095A (zh) | 2024-08-20 |
| KR20240153302A (ko) | 2024-10-22 |
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