WO2017074061A1 - Procédé de production d'un diol à chaîne lourde - Google Patents

Procédé de production d'un diol à chaîne lourde Download PDF

Info

Publication number
WO2017074061A1
WO2017074061A1 PCT/KR2016/012170 KR2016012170W WO2017074061A1 WO 2017074061 A1 WO2017074061 A1 WO 2017074061A1 KR 2016012170 W KR2016012170 W KR 2016012170W WO 2017074061 A1 WO2017074061 A1 WO 2017074061A1
Authority
WO
WIPO (PCT)
Prior art keywords
gene
fatty
fatty alcohol
recombinant microorganism
genes
Prior art date
Application number
PCT/KR2016/012170
Other languages
English (en)
Korean (ko)
Inventor
안정오
이홍원
장민정
김천석
박규연
Original Assignee
한국생명공학연구원
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 한국생명공학연구원 filed Critical 한국생명공학연구원
Priority to US15/771,799 priority Critical patent/US11091741B2/en
Priority to EP16860244.9A priority patent/EP3378940B1/fr
Priority claimed from KR1020160141017A external-priority patent/KR101903551B1/ko
Publication of WO2017074061A1 publication Critical patent/WO2017074061A1/fr

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/70Vectors or expression systems specially adapted for E. coli
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00Preparation of oxygen-containing organic compounds
    • C12P7/02Preparation of oxygen-containing organic compounds containing a hydroxy group
    • C12P7/04Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic
    • C12P7/18Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic polyhydric

Definitions

  • the present invention relates to a method for producing heavy chain diols, and more particularly, the fatty alcohol dehydrogenase and / or fatty alcohol oxidase genes in the ⁇ -oxidative metabolic pathway are removed and optionally fat
  • a method for producing heavy chain diols from alcohols or alkanes derived from fatty acids by culturing recombinant microorganisms in which the aldehyde dehydrogenase gene has been removed and the ⁇ -oxidation metabolic pathway related gene has been removed.
  • Bioplatform compounds are produced through biological or chemical conversion based on biomass-derived raw materials, and are used for synthesis of polymer monomers and new materials.
  • medium chain diols are used as monomers of polyesters, and polyesters are widely used for various purposes, including fibers, films, and combinations due to their excellent properties.
  • polyethylene terephthalate obtained by polycondensation of ethylene glycol and terephthalic acid is used in many applications because of its excellent mechanical strength, chemical properties, and the like, and has been mass produced in the world as the most suitable synthetic fiber for medical use.
  • polytrimethylene terephthalate as a raw material of 1,3-propanediol and terephthalic acid has recently been developed a low-cost 1,3-propanediol synthesis method, the market tends to increase, excellent elastic modulus recovery, and a Young's modulus The development as a soft touch medical use utilizing the low polymer characteristic is anticipated.
  • polyester derived from biomass resources has been attracting attention due to concern about higher and depletion of petroleum resources.
  • heavy chain diols can be achieved by biological methods through chemical synthesis or microbial fermentation.
  • the use of such biological methods requires the development of new strains and optimization of fermentation processes using metabolic engineering techniques.
  • strains capable of producing heavy chain diols may be microorganisms having a ⁇ -oxidative metabolic pathway and a ⁇ -oxidative metabolic pathway, for example, Klebsiella oxytoca and Klebsiella pneumoniae. pneumoniae, aerobacter aerogenes, and recombinant Saccharomyces cerevisiae are known to be able to produce 2,3-butanediol with high yield and high productivity.
  • the present invention removes fatty alcohol dehydrogenase and / or fatty alcohol oxidase related genes in the ⁇ -oxidative metabolic pathway, optionally removes fatty aldehyde dehydrogenase gene, and also eliminates ⁇ -oxidative metabolic pathway related genes. It is an object of the present invention to provide a method for producing heavy chain diols from alcohols or alkanes derived from fatty acids by culturing the recombinant microorganisms and the recombinant microorganisms.
  • the present invention removes one or more genes selected from the group consisting of fatty alcohol dehydrogenase and fatty alcohol oxidase in the ⁇ -oxidation metabolic pathway, and optionally the fatty aldehyde dehydrogenase gene It also provides a recombinant microorganism that has been removed, and in which genes related to ⁇ -oxidation metabolic pathways have been removed.
  • the fatty alcohol dehydrogenase, fatty alcohol oxidase, fatty aldehyde dehydrogenase and ⁇ -oxidation pathway related genes are preferably all homologous genes present in the microorganism are removed. But it is not limited thereto. According to another embodiment of the present invention, the fatty alcohol dehydrogenase, fatty alcohol oxidase, fatty aldehyde dehydrogenase and ⁇ -oxidation metabolic pathway related genes are preferably removed from some homologous genes present in the microorganism. But it is not limited thereto.
  • the fatty alcohol dehydrogenase gene may be selected from the group consisting of ADH1, ADH2, ADH3, ADH4, ADH5, ADH6, ADH7, ADH8 and FADH gene, but is not limited thereto.
  • the fatty alcohol oxidase gene may be a FAO gene, but is not limited thereto.
  • the fatty aldehyde dehydrogenase gene may be a gene selected from the group consisting of FALDH1, FALDH2, FALDH3 and FALDH4 genes, but is not limited thereto.
  • the ⁇ -oxidation pathway related gene may be an acyl-CoA oxidase gene, but is not limited thereto.
  • the acyl-CoA oxidase gene may be selected from the group consisting of ACO1, ACO2, ACO3, ACO4, ACO5 and ACO6 genes, but is not limited thereto.
  • the microorganism may be yeast or E. coli, but is not limited thereto.
  • the yeast may be a yeast selected from the group consisting of genus Yarrowia, genus Saccharomyces, Pichia and Candida, but is not limited thereto.
  • the yeast of the genus Yarrowia may be, but is not limited to Yarrowia repolitica.
  • the present invention (1) at least one gene selected from the group consisting of fatty alcohol dehydrogenase and fatty alcohol oxidase in the ⁇ -oxidation metabolic pathway is removed, optionally the fatty aldehyde dehydrogenase gene is removed, In addition, preparing a recombinant microorganism from which the gene related to the ⁇ -oxidation metabolic pathway has been removed; And (2) provides a method for producing a heavy chain diol comprising the step of culturing the substrate to the recombinant microorganism.
  • the substrate may be selected from the group consisting of alcohols and alkanes derived from fatty acids, but is not limited thereto.
  • the alcohol, alkanes and heavy chain diols derived from fatty acids may each have 5 to 30 carbon atoms, preferably 6 to 20 carbon atoms, more preferably 8 to 16 carbon atoms, but are not limited thereto. no.
  • the alkanes may be dodecane, but is not limited thereto.
  • the heavy chain diol may be 1,12-dodecanediol, but is not limited thereto.
  • the recombinant microorganism of the present invention removes the fatty alcohol dehydrogenase and / or fatty alcohol oxidase genes in the ⁇ -oxidative metabolic pathway, optionally the fatty aldehyde dehydrogenase gene, and also the ⁇ -oxidative metabolic pathway related genes. Can be removed to prevent further oxidation of the fatty alcohol and ⁇ -oxidation metabolism to produce heavy chain diols in high yield.
  • FIG. 2 is a process for preparing a recombinant microorganism of the present invention in which the fatty alcohol dehydrogenase, fatty alcohol oxidase gene and fatty aldehyde dehydrogenase gene related to ⁇ -oxidation and the acyl-CoA oxidase gene associated with ⁇ -oxidation are removed. It is shown schematically.
  • Figure 3 schematically shows a vector having a ura3 gene to be used as a selection marker for gene knockout for strain improvement and a pop-out for removing the ura3 gene after the knockout cassette insertion.
  • Figure 4 is a schematic diagram showing the manufacturing process of the knock-out cassette used in the production of the transformed microorganism of the present invention.
  • 5 is a graph showing the types of genes knocked out in the transformed microorganism of the present invention.
  • 6 is a graph showing the amount of heavy chain diols produced from alkanes as substrates of the transformed microorganism of the present invention.
  • FIG. 7 is a graph showing the amount of heavy chain diols produced from alkanes as substrates when the Y4-20 strain of the present invention is cultured in a flask.
  • the present invention removes one or more genes selected from the group consisting of fatty alcohol dehydrogenases and fatty alcohol oxidases in the ⁇ -oxidation metabolic pathway, optionally removes fatty aldehyde dehydrogenase genes, and also ⁇ -oxidation metabolism.
  • fatty alcohol dehydrogenases and fatty alcohol oxidases in the ⁇ -oxidation metabolic pathway, optionally removes fatty aldehyde dehydrogenase genes, and also ⁇ -oxidation metabolism.
  • ⁇ -oxidation refers to a metabolic process in which a methyl group terminal of a fatty acid is oxidized to form a dicarboxylic acid
  • ⁇ -oxidation means that a ⁇ -site carbon atom is oxidized in a carboxy group. It is a metabolic process that releases acetyl CoA and gradually breaks down into fatty acids with two carbon atoms each time.
  • the concepts of ⁇ -oxidation and ⁇ -oxidation and the enzymes involved in this metabolic process are well known to those skilled in the biochemistry art.
  • ⁇ -hydroxy fatty acid is first produced by the action of cytochrome P450 and NADPH-cytochrome P450 reductase, and the ⁇ -hydroxy fatty acid is ⁇ -aldehyde fatty acid is produced by the action of fatty alcohol dehydrogenase and fatty alcohol oxidase, and the ⁇ -aldehyde fatty acid is produced by the action of fatty aldehyde dehydrogenase.
  • acyl-CoA oxidase produces fatty acids having two carbon atoms (see FIG. 1).
  • the fatty alcohol dehydrogenase and fatty alcohol oxidase gene, and the fatty aldehyde dehydrogenase gene that can be selectively removed is that all homologous genes present in the microorganism are removed Preferably, however, recombinant microorganisms in which some of these genes have been removed may also be applied in the present invention.
  • the fatty alcohol dehydrogenase gene may be selected from the group consisting of ADH1, ADH2, ADH3, ADH4, ADH5, ADH6, ADH7, ADH8 and FADH gene, but is not limited thereto.
  • the ADH1, ADH2, ADH3, ADH4, ADH5, ADH6, ADH7, ADH8 and FADH gene may include a base sequence consisting of SEQ ID NO: 1 and SEQ ID NO: 9, but is not limited thereto. no.
  • the fatty alcohol oxidase gene may be a FAO gene, but is not limited thereto.
  • the FAO gene may include a nucleotide sequence consisting of SEQ ID NO: 10, but is not limited thereto.
  • the fatty aldehyde dehydrogenase gene may be selected from the group consisting of FALDH1, FALDH2, FALDH3 and FALDH4 genes, but is not limited thereto.
  • the FALDH1, FALDH2, FALDH3 and FALDH4 genes may include, but are not limited to, nucleotide sequences consisting of SEQ ID NO: 11 and SEQ ID NO: 14, respectively.
  • the ⁇ -oxidation metabolic pathway related gene is preferably all homologous genes present in the microorganism is removed, but in some cases, the recombinant microorganism from which some of the genes are removed Can be applied.
  • the ⁇ -oxidation pathway related gene is an acyl-CoA oxidase gene, and the acyl-CoA oxidase gene may be selected from the group consisting of ACO1, ACO2, ACO3, ACO4, ACO5 and ACO6 genes, but is not limited thereto. No (see Figure 2).
  • the ACO1, ACO2, ACO3, ACO4, ACO5 and ACO6 gene may include a base sequence consisting of SEQ ID NO: 15 and SEQ ID NO: 20, but is not limited thereto.
  • genes selected from the fatty alcohol dehydrogenase gene, fatty alcohol oxidase gene, fatty aldehyde dehydrogenase and acyl-CoA oxidase are removed using conventional genetic recombination techniques known in the art.
  • Recombinant microorganisms can be prepared.
  • the term "removal" is not only a part or all of the gene is physically removed, but also a state in which a protein is not made from mRNA transcribed from the gene and the protein expressed from the gene function The state of not being able to be used is also used in the sense of comprehensive inclusion.
  • Genetic recombination techniques that can be used include, but are not limited to, methods such as transformation, transduction, transfection, microinjection, electroporation, and the like. .
  • any microorganism that can be used may be used without limitation any microorganism having both ⁇ -oxidation and ⁇ -oxidation metabolic processes, for example, eukaryotes including yeast and prokaryotes including E. coli are used. Can be.
  • the microorganism is preferably using yeast, and as the yeast Yarrowia sp., Saccharomyces sp., Pichia sp. Yeasts such as Candida sp.
  • Yarrowia lipolytica Candida tropicalis, Candida infanticola
  • saccharo Preference is given to using Saccharomyces cerevisiae, Pichia alcoholophia or Candida mycoderma, more preferably to Yarrowia repolitica.
  • cytochrome P450 As described above, in the case of microorganisms in which the fatty alcohol dehydrogenase, fatty alcohol oxidase gene and ⁇ -oxidation pathway related gene, and optionally the fatty aldehyde dehydrogenase gene are removed, cytochrome P450 and The action of NADPH-cytochrome P450 reductase oxidizes either end to form a primary alcohol, but prevents further oxidation because the fatty alcohol dehydrogenase gene and fatty alcohol oxidase gene are removed. do.
  • the primary alcohol formed as described above becomes a substrate again, and the other end is oxidized by the action of cytochrome P450 and NADPH-cytochrome P450 reductase to form a diol, which is a secondary alcohol.
  • cytochrome P450 and NADPH-cytochrome P450 reductase to form a diol, which is a secondary alcohol.
  • one or more genes selected from the group consisting of fatty alcohol dehydrogenase and fatty alcohol oxidase in the ⁇ -oxidation metabolic pathway are removed, optionally the fatty aldehyde dehydrogenase gene is removed, and also ⁇ -oxidation metabolism Preparing a recombinant microorganism from which pathway related genes have been removed;
  • the fatty alcohol dehydrogenase and / or fatty alcohol oxidase genes in the ⁇ -oxidative metabolic pathway are removed, optionally the fatty aldehyde dehydrogenase gene is removed, and the ⁇ -oxidative metabolic pathway related genes are also removed.
  • the recombinant microorganisms from which the polysaccharides have been removed can be used to prevent heavy oxidation and ⁇ -oxidation metabolism of fatty alcohols to produce heavy chain diols in high yield.
  • the fatty alcohol dehydrogenase, fatty alcohol oxidase, fatty aldehyde dehydrogenase and ⁇ -oxidation pathway related genes are preferably all homologous genes present in the microorganism, but in some cases some of them Recombinant microorganisms having been removed can also be applied in the present invention.
  • any microorganism that can be used may be used without limitation any microorganism having both ⁇ -oxidation and ⁇ -oxidation metabolic processes, for example, eukaryotes including yeast and prokaryotes including E. coli are used. Can be.
  • the microorganism is preferably using yeast, and yeasts such as Yarrowia genus, Saccharomyces genus, Pichia genus, Candida genus and the like may be used without limitation.
  • Yarrowia Lipolitica Saccharomyces cerevisiae, Candida Tropicalis, Candida Infanticola, Pichia Alcoholopia or Candida Mycoderma, and more preferably Yarrowia Lipolitica. desirable.
  • genes selected from the fatty alcohol dehydrogenase gene, fatty alcohol oxidase gene, fatty aldehyde dehydrogenase and acyl-CoA oxidase are removed using conventional genetic recombination techniques known in the art. Recombinant microorganisms can be prepared.
  • the term "removal" is not only a part or all of the gene is physically removed, but also a state in which a protein is not made from mRNA transcribed from the gene and the protein expressed from the gene function The state of not being able to be used is also used in the sense of comprehensive inclusion.
  • diol refers to a compound containing two hydroxyl groups (-OH group), “heavy chain diol” is 5 to 30 carbon atoms, preferably 6 to 20 carbon atoms, more preferably carbon atoms It is used with the meaning including all the diol compounds which have 8-16.
  • the substrate of step (2) may be selected from the group consisting of alcohols and alkanes derived from fatty acids, but is not limited thereto.
  • the alcohol derived from the fatty acid may be an alcohol having 5 to 30 carbon atoms, preferably 6 to 20 carbon atoms, more preferably 8 to 16 carbon atoms, but is not limited thereto.
  • the alkanes may be used alkanes having 5 to 30 carbon atoms, preferably 6 to 20 carbon atoms, more preferably 8 to 16 carbon atoms, but are not limited thereto.
  • the alkanes may be dodecane, but is not limited thereto.
  • the heavy chain diol may be 1,12-dodecanediol, but is not limited thereto.
  • a vector having a ura3 gene to be used as a selection marker for gene knock-out for strain improvement and a pop-out for removing the ura3 gene after insertion of the knock-out cassette was constructed (FIG. 3).
  • the primers used to PCR the pop-out region and ura3 in two pieces are shown in Table 3.
  • the cultured cells were scraped with a loop and vortexed in 100 ⁇ l of one-step buffer (45% PEG4000, 100 mM DTT, 0.1 L LiAc, 25 ⁇ g single-strand carrier DNA), followed by addition of a knock-out cassette (1 ng or more).
  • a knock-out cassette (1 ng or more).
  • the cultured samples were loaded into selection medium (YNB w / o amino acid 6.7g / L, Glucose 20g / L) and incubated at 30 ° C. for 48 hours to select the inserted strain. Then, it was confirmed by PCR using the fries included in the gene deletion of Table 2 to confirm that the cassettes are correctly inserted on the genome of the selected strain.
  • the strain into which the cassette was inserted went through a pop-out process to proceed with the insertion of another cassette.
  • 200 ⁇ l of the culture medium was mixed with 5 ′ FOA medium (YNB w / o amino acid 6.7g / L, Glucose 20g / L, 5 'FOA).
  • 5 ′ FOA medium YNB w / o amino acid 6.7g / L, Glucose 20g / L, 5 'FOA.
  • the strain to be tested was inoculated in 2 ml of YPD medium (Bacto Laboratories, Yeast extract 10g / L, peptone 20g / L, glucose 20g / L) the day before at 30 °C, 200rpm.
  • 2 ml of growth stage medium (pH 6.0) having the composition shown in Table 5 was placed in a 24-well plate, and then inoculated with 1% of the pre-cultured culture, followed by incubation at 30 ° C. and 450 rpm for one day in a plate stirrer.
  • the Y1-28 and Y1-36 strains that only knocked out the ⁇ -oxidation metabolism related gene and the fatty aldehyde dehydrogenase gene could not produce 1,12-dodecanediol from the substrate dodecane, but the fat
  • the Y1-36 strain additionally knocked out the alcohol oxidase gene and the Y4-2, Y4-20 and Y4-30 strains additionally knocked out the fatty alcohol oxidase gene and the fatty alcohol dehydrogenase gene were all excellent. It showed the ability to synthesize 1,12-dodecanediol (FIG. 6).
  • the Y4-20 strain showed a 1,12-dodecanediol synthesis capacity of about 18 mg / L when cultured in the flask (Fig. 7).
  • a sample analysis experiment using the Y4-20 strain was performed.

Abstract

La présente invention concerne un procédé de production d'un diol à chaîne lourde, et plus particulièrement des micro-organismes recombinés dans lesquels les gènes de l'alcool gras déshydrogénase et/ou de l'alcool gras oxydase dans la voie du métabolisme ω-oxydatif sont éliminés, les gènes de l'aldéhyde gras déshydrogénase sont éventuellement éliminés, et les gènes liés à la voie du métabolisme β-oxydatif sont éliminés, et un procédé de production d'un diol à chaîne lourde à partir d'un alcool ou d'un alcane dérivé d'un acide gras par culture des micro-organismes recombinés. Les micro-organismes recombinés selon l'invention peuvent produire un diol à chaîne lourde à un rendement élevé en empêchant la poursuite de l'oxydation et du métabolisme β-oxydatif des alcools gras.
PCT/KR2016/012170 2015-10-27 2016-10-27 Procédé de production d'un diol à chaîne lourde WO2017074061A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US15/771,799 US11091741B2 (en) 2015-10-27 2016-10-27 Method for producing medium chain diol
EP16860244.9A EP3378940B1 (fr) 2015-10-27 2016-10-27 Procédé de production d'un diol à chaîne lourde

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20150149251 2015-10-27
KR10-2015-0149251 2015-10-27
KR10-2016-0141017 2016-10-27
KR1020160141017A KR101903551B1 (ko) 2015-10-27 2016-10-27 중쇄 디올의 생산 방법

Publications (1)

Publication Number Publication Date
WO2017074061A1 true WO2017074061A1 (fr) 2017-05-04

Family

ID=58631851

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2016/012170 WO2017074061A1 (fr) 2015-10-27 2016-10-27 Procédé de production d'un diol à chaîne lourde

Country Status (1)

Country Link
WO (1) WO2017074061A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101145405B1 (ko) * 2008-12-03 2012-05-16 한국생명공학연구원 글리세롤 산화경로가 차단된 1、3―프로판디올 생산 변이체
US8530206B2 (en) * 2008-05-21 2013-09-10 Ecover Coordination Center N.V. Method for the production of medium-chain sophorolipids
KR20140142518A (ko) * 2013-06-04 2014-12-12 서강대학교산학협력단 (a) wabG 유전자가 불활성화 되어 있고 (b) budR 유전자가 과발현된 2,3-부탄다이올 생산용 재조합 균주
KR20150039055A (ko) * 2013-10-01 2015-04-09 삼성전자주식회사 대장균 내에서 1,4-부탄디올의 생합성에 사용되는 효소, 이의 변이체 및 이를 이용한 1,4-부탄디올 생산방법

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8530206B2 (en) * 2008-05-21 2013-09-10 Ecover Coordination Center N.V. Method for the production of medium-chain sophorolipids
KR101145405B1 (ko) * 2008-12-03 2012-05-16 한국생명공학연구원 글리세롤 산화경로가 차단된 1、3―프로판디올 생산 변이체
KR20140142518A (ko) * 2013-06-04 2014-12-12 서강대학교산학협력단 (a) wabG 유전자가 불활성화 되어 있고 (b) budR 유전자가 과발현된 2,3-부탄다이올 생산용 재조합 균주
KR20150039055A (ko) * 2013-10-01 2015-04-09 삼성전자주식회사 대장균 내에서 1,4-부탄디올의 생합성에 사용되는 효소, 이의 변이체 및 이를 이용한 1,4-부탄디올 생산방법

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PARK ET AL.: "Metabolic Engineering of Escherichia Coli for the Production of Medium-chain-length Polyhydroxyalkanoates Rich in Specific Monomers", FEMS MICROBIOLOGY LETTERS, vol. 214, 2002, pages 217 - 222, XP055227754 *

Similar Documents

Publication Publication Date Title
Cernak et al. Engineering Kluyveromyces marxianus as a robust synthetic biology platform host
KR101149566B1 (ko) Nadph를 소비하는 생합성 경로에 최적화시킨 미생물 균주
US8236994B2 (en) Process for the biological production of 1,3-propanediol from glycerol with high yield
US8158391B2 (en) Production of an α-carboxyl-ω-hydroxy fatty acid using a genetically modified Candida strain
Kim et al. Combinatorial design of a highly efficient xylose-utilizing pathway in Saccharomyces cerevisiae for the production of cellulosic biofuels
US8445243B2 (en) Hexose-pentose cofermenting yeast having excellent xylose fermentability and method for highly efficiently producing ethanol using the same
UA76690C2 (uk) Дріжджі, що зброджують ксилозу у етанол (варіанти), плазмідний вектор та спосіб зброджування ксилози у етанол
WO2019203436A1 (fr) Levure résistante aux acides avec voie de production d'éthanol supprimée et procédé de production d'acide lactique l'utilisant
TWI450963B (zh) 具高木醣消耗率之分離酵母菌株及使用該菌株製造酒精之方法
JP7164112B2 (ja) 重鎖アミノカルボン酸の生産方法
WO2017074061A1 (fr) Procédé de production d'un diol à chaîne lourde
Qiu et al. Kluyveromyces as promising yeast cell factories for industrial bioproduction: From bio-functional design to applications
US11091741B2 (en) Method for producing medium chain diol
US20190338256A1 (en) Redox balancing in yeast
TW201249992A (en) A method for preparing a xylose-utilizing strain of Saccharomyces cerevisiae and the Saccharomyces cerevisiae
WO2017074063A1 (fr) Procédé de production d'un acide aminocarboxylique à chaîne lourde
US9127323B2 (en) Isolated yeast strain having high xylose consumption rate and process for production of ethanol using the strain
US20200131538A1 (en) Microorganism with stabilized copy number of functional dna sequence and associated methods
WO2017074065A1 (fr) Procédé de production d'une diamine à chaîne lourde
KR101903552B1 (ko) 중쇄 디아민의 생산 방법
EP3802783A1 (fr) Microorganismes et production de produits chimiques fins
US20230227861A1 (en) Gene duplications for crabtree-warburg-like aerobic xylose fermentation
WO2021112641A1 (fr) Souche recombinante pour la production de diols à chaîne lourde et procédé de production de diols à chaîne lourde faisant appel à celle-ci
CN102268431A (zh) 乳清酸核苷-5’-磷酸脱羧酶启动子及应用和构建体与载体
Kelso Foundational Tools for Synthetic Methylotrophy in Saccharomyces cerevisiae

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16860244

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 15771799

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2016860244

Country of ref document: EP