WO2022265429A1 - 발효액으로부터 목적한 화합물을 수득하는 방법 - Google Patents
발효액으로부터 목적한 화합물을 수득하는 방법 Download PDFInfo
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- WO2022265429A1 WO2022265429A1 PCT/KR2022/008552 KR2022008552W WO2022265429A1 WO 2022265429 A1 WO2022265429 A1 WO 2022265429A1 KR 2022008552 W KR2022008552 W KR 2022008552W WO 2022265429 A1 WO2022265429 A1 WO 2022265429A1
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- fermentation broth
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- 238000000855 fermentation Methods 0.000 title claims abstract description 164
- 230000004151 fermentation Effects 0.000 title claims abstract description 164
- 238000000034 method Methods 0.000 title claims abstract description 63
- 150000001875 compounds Chemical class 0.000 title claims abstract description 47
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- 229920002521 macromolecule Polymers 0.000 claims abstract description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 14
- 239000000126 substance Substances 0.000 claims abstract description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 48
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- 102000004169 proteins and genes Human genes 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- ALRHLSYJTWAHJZ-UHFFFAOYSA-N 3-hydroxypropionic acid Chemical compound OCCC(O)=O ALRHLSYJTWAHJZ-UHFFFAOYSA-N 0.000 description 140
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- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 10
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- 244000005700 microbiome Species 0.000 description 7
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- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 3
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- 241000588724 Escherichia coli Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000003011 anion exchange membrane Substances 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
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- -1 3-HP calcium salt Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
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- 238000012258 culturing Methods 0.000 description 1
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- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
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- 239000010452 phosphate Substances 0.000 description 1
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/47—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/14—Ultrafiltration; Microfiltration
- B01D61/145—Ultrafiltration
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/14—Ultrafiltration; Microfiltration
- B01D61/147—Microfiltration
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/42—Electrodialysis; Electro-osmosis ; Electro-ultrafiltration; Membrane capacitive deionization
- B01D61/422—Electrodialysis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/42—Electrodialysis; Electro-osmosis ; Electro-ultrafiltration; Membrane capacitive deionization
- B01D61/44—Ion-selective electrodialysis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/58—Multistep processes
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J47/00—Ion-exchange processes in general; Apparatus therefor
- B01J47/014—Ion-exchange processes in general; Apparatus therefor in which the adsorbent properties of the ion-exchanger are involved, e.g. recovery of proteins or other high-molecular compounds
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
-
- 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
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
- C12P7/04—Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic
- C12P7/18—Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic polyhydric
-
- 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
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
- C12P7/52—Propionic acid; Butyric acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2311/00—Details relating to membrane separation process operations and control
- B01D2311/26—Further operations combined with membrane separation processes
- B01D2311/2623—Ion-Exchange
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2311/00—Details relating to membrane separation process operations and control
- B01D2311/26—Further operations combined with membrane separation processes
- B01D2311/2642—Aggregation, sedimentation, flocculation, precipitation or coagulation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2311/00—Details relating to membrane separation process operations and control
- B01D2311/26—Further operations combined with membrane separation processes
- B01D2311/2673—Evaporation
Definitions
- the present invention relates to a method for obtaining a desired compound from a fermentation broth.
- 3-hydroxypropionic acid (3-HP) can be produced through a chemical synthesis process and a microbial fermentation process, and a method for producing 3-HP using bacteria such as Escherichia coli and Klebsiella has recently been studied.
- Korean Patent Publication No. 10-2020-0051375 discloses a technique for producing 3-HP using a microorganism transformed with a specific gene.
- the present invention relates to a method for isolating and obtaining 3-HP from a fermentation broth containing 3-HP produced by microbial culture.
- An object of the present invention is to provide a method for obtaining a target compound from a fermentation broth.
- a target compound can be separated from a fermentation broth in high yield.
- 1 is a schematic diagram showing a method for obtaining the compound of the present invention.
- Figure 2 is a test result of separating insoluble substances from the fermentation broth through a microfilter.
- Figure 3 is the result of confirming the peaks of 3-HP, 1,3-propanediol and glycerol in the fermentation broth through single column chromatography.
- Figure 4 shows the process of precipitating and removing calcium ions in the fermentation broth.
- Figure 5 shows the change in ion concentration in the fermentation broth according to ion exchange.
- FIG. 6 shows a process of removing ions in the fermentation broth through ion exchange.
- any step may be repeated two or more times.
- the step (a) may be performed through at least one selected from the group consisting of evaporation, concentration and distillation.
- Step (c) may be performed by the following (c)' or (c)'':
- (c)'' A process of treating the fermentation broth with at least one selected from the group consisting of electrodialysis, ion exchange, and chromatography.
- the insoluble matter may include cells, and the macromolecules may be proteins, polysaccharides, or lipids. At this time, at least a part of the insoluble material may be removed, at least a part of the macromolecule may be removed, or at least a part of the insoluble material and at least a part of the macromolecule may be removed from the fermentation broth. At this time, after removing at least a portion of the insoluble matter from the fermentation broth, at least a portion of the macromolecules may be removed. Alternatively, at this time, after removing at least some of the macromolecules from the fermentation broth, at least some of the insoluble materials may be removed.
- the target compound may be an organic acid produced by microbial fermentation, preferably 3-hydroxypropionic acid (3-HP).
- the carbon source of (b) may be glycerol or glucose.
- the alcohol of (b) may be an alcohol produced by microbial fermentation, such as 1,3-propanediol.
- the method for obtaining the compound of the present invention is to first remove at least a portion of the insoluble matter from the fermentation broth and remove at least a portion of the macromolecules, and then (a) increase the concentration of the desired compound in the fermentation broth. (b) reducing the concentration of residual carbon source or alcohol in the fermentation broth, (c)': acid treatment of the fermentation broth to precipitate and remove ionic components (c)'': electrodialysis, ion exchange of the fermentation broth and chromatography, and secondly, (a) increasing the concentration of the target compound in the fermentation broth and then recovering the target compound to obtain the compound.
- the fermentation broth may be a fermentation broth prepared by the following process 1: fermentation broth preparation step.
- the step of removing at least a part of the insoluble matter or macromolecule from the fermentation broth may be the following process 2: separation of insoluble matter or the following process 3: macromolecule removal and decolorization step.
- the first (a) step of increasing the concentration of the target compound in the fermentation broth may be the following step 4: increasing the concentration of 3-HP in the fermentation broth.
- the (b) step of reducing the concentration of the remaining carbon source or alcohol in the fermentation broth may be the following Step 5: reducing the concentration of glycerol or alcohol in the fermentation broth.
- the step (c)': acid treatment of the fermentation broth to precipitate and remove ionic components may be the following step 6: reducing ionic components in the fermentation broth (precipitation and filtration).
- Step 7 Reducing ionic components in the fermentation broth (electrodialysis and ion exchange) can be
- the second (a) step of increasing the concentration of the target compound in the fermentation broth may be the following step 8: increasing the concentration of 3-HP in the fermentation broth.
- the step of recovering the target compound may be the following process 9: recovery step.
- Process 1 fermentation broth preparation step
- the method for obtaining the compound of the present invention may include a fermentation broth preparation step.
- the fermentation broth may be a fermentation broth (fermentation broth) fermented using microorganisms, that is, a culture broth.
- the culture medium may further include other components other than 3-HP and salts thereof.
- the culture medium may include a calcium salt of 3-HP.
- the other components may be a carbon source (eg, glycerol, etc.), an organic acid (eg, acetic acid, etc.), a salt (eg, sulfate, phosphate, etc.), an alcohol (eg, diol), sugar, calcium, etc. used for culturing microorganisms.
- the concentration of 3-HP or a salt thereof in the fermentation broth is, for example, about 10,000 to 200,000 ppm, for example about 12,000 to 190,000 ppm, for example about 15,000 to 180,000 ppm, for example about 20,000 to 150,000 ppm, for example about 25,000 to 130,000 ppm, for example about 30,000 to 110,000 ppm.
- the concentration of 3-HP or a salt thereof in the fermentation broth is, for example, about 10,000 ppm or more, such as about 12,000 ppm or more, such as about 15,000 ppm or more, such as about 20,000 ppm or more, such as about 25,000 ppm or more, such as about 30,000 ppm may be ideal
- the concentration of 3-HP or a salt thereof in the fermentation broth is, for example, 200,000 ppm or less, such as about 190,000 ppm or less, such as about 180,000 ppm or less, such as about 150,000 ppm or less, such as about 130,000 ppm or less, such as about 110,000 ppm or less can
- the step of adjusting the pH of the fermentation broth may be further included.
- the pH can be adjusted by treating the fermentation broth with acid or alkali.
- the type of acid or alkali is not particularly limited, and a conventional acid or alkali used when adjusting the pH of a fermentation broth may be used.
- the desired pH may be properly adjusted differently depending on the type of compounds to be separated from 3-HP and the method of the subsequent separation process.
- the method for obtaining the compound of the present invention may include separating at least a portion of insoluble matter from the fermentation broth.
- the fermentation broth may be a fermentation broth prepared in step 1 or a fermentation broth that has passed through steps 1 and 3, that is, a treatment solution.
- the insoluble matter may be microorganisms, ie, cells, solids, and the like.
- Separation of the insoluble matter may be performed using a centrifugal separator, a filtration process, and the like, but is not particularly limited. As a result, microorganisms, that is, cells, can be separated from the fermentation broth.
- microfiltration can remove microorganisms and solids in the fermentation broth.
- Microfiltration may be performed by passing the fermentation broth through a polymer or ceramic membrane having a pore size of 0.04 to 5 ⁇ m.
- the microfiltration operation may be configured in two or more stages according to the tendency of flux (unit area of membrane and throughput per unit time) to decrease.
- water may be additionally added to the fermentation broth to increase the recovery rate at the point where the flux is significantly lowered.
- a method for obtaining a compound of the present invention may include isolating at least some of the macromolecules from the fermentation broth.
- the step of separating at least some of the macromolecules from the fermentation broth may include removing and decolorizing the macromolecules from the fermentation broth.
- the fermentation broth may be a fermentation broth prepared in step 1 or a fermentation broth that has passed through steps 1 and 2, that is, a treatment solution.
- the macromolecules may be proteins, polysaccharides, lipids, and the like.
- the macromolecule removal and decolorization step may be performed by filtering after mixing activated carbon and a filter aid in the fermentation broth.
- macromolecule removal and decolorization effects may be obtained by mixing activated carbon and filter aids (diatomaceous earth, white clay, etc.) with the fermentation broth from which microorganisms are removed and filtering (eg, filter press, etc.).
- the filtration may use a filtration method of powder particles that can be commonly used (eg, filter press, drum filter, candle filter, leaf filter, etc.) and is not particularly limited.
- activated carbon By removing macromolecules such as some proteins and polysaccharides through the addition of activated carbon, it is possible to suppress the generation of adhesive substances that may occur in the process of increasing the 3-HP concentration.
- activated carbon not only powdered activated carbon but also granular activated carbon can be applied. For example, after adding 0.1 to 2 wt% of powdered activated carbon based on the weight of the fermentation broth, stirring at 30 to 80 ° C. for 1 to 5 hours and then filtering, the color of the fermentation broth could be removed. After mixing 1.5% of powdered activated carbon in the fermentation broth, stirring at 40 ° C. for 1 hour and filtering, the APHA (American Public Health Association) color value of the fermentation broth was 2.7. In addition, when granular activated carbon is applied at a mass fraction of 5 to 15% relative to the weight of the fermentation broth, similar decolorization performance to that of powdered activated carbon can be expected. .
- the macromolecule removal and decolorization steps may be performed through membrane separation of the treatment liquid.
- the membrane separation method may be ultrafiltration or nanofiltration, and in this case, macromolecular removal and decolorization effects may be obtained without an additional decolorization process.
- ultrafiltration applies an ultrafiltration membrane having a Molecular Weight of Cut-Off (MWCO) of 5000 to 100,000 Da, followed by a nanofiltration membrane of 150 to 300 Da, thereby minimizing loss of 3-HP salt while minimizing protein, polysaccharide, lipids Only macromolecules such as
- Step 4 Increasing the concentration of 3-HP in the fermentation broth
- the method for obtaining the compound of the present invention may include increasing the concentration of 3-HP in the fermentation broth.
- the fermentation broth of step 4 may be a treatment solution that has passed through steps of step 2 and/or step 3.
- the fermentation broth in step 4 may be a treatment solution that has undergone step 2 and/or step 3 and then passed through one or more steps of steps 5 to 8.
- the concentration of 3-HP can be increased by methods such as At this time, the concentration may be increased to 100 to 500 g of 3-HP equivalent per 1 L of the fermentation broth.
- the concentration increase may be accompanied by pressure control, and may be performed under appropriate pressure, such as about 20 to 300 mbar, such as about 25 to 280 mbar, such as about 30 to 250 mbar, such as about 50 to 200 mbar based on absolute pressure. , such as about 70 to 190 mbar, such as about 80 to 180 mbar.
- the concentration increasing step may be performed at, for example, about 20 mbar or less, such as about 25 mbar or less, such as about 30 mbar or less, such as about 50 mbar or less, such as about 70 mbar or less, such as about 80 mbar or less.
- the concentration increasing step may be performed at, for example, about 300 mbar or less, such as about 280 mbar or less, such as about 250 mbar or less, such as about 200 mbar or less, such as about 190 mbar or less, such as about 180 mbar or less.
- Process 5 reducing the concentration of glycerol or alcohol in the fermentation broth
- the method for obtaining the compound of the present invention may include reducing the concentration of glycerol or alcohol in the fermentation broth.
- the fermentation broth of step 5 may be a treatment solution that has passed through steps of step 2 and/or step 3.
- the fermentation broth of step 5 may be a treatment solution that has been subjected to step 4 or at least one of steps 6 to 8 after step 2 and/or step 3.
- the glycerol may be a carbon source used during microbial culture
- the alcohol may be a microbial culture product such as 1,3-propanediol (1,3-PDO).
- the concentration of glucose in the fermentation broth may be reduced by step 5.
- the concentration of glycerol or alcohol in the fermentation broth may be reduced by applying chromatography using an ion exchange resin (eg, Simulated Moving Bed (SMB) chromatography), which is achieved by using 3-HP obtained by the method of the present invention. It is an important factor affecting the quality of a product when performing polymer polymerization.
- SMB Simulated Moving Bed
- the mobile phase is injected together with the feed to obtain a fraction enriched in one or more 3-HP (fraction A) and a fraction enriched in one or more compounds other than 3-HP (fraction B).
- Process 6 step of reducing ionic components in fermentation broth (precipitation and filtration)
- a method for obtaining the compound of the present invention may include reducing the ionic component in the fermentation broth.
- the fermentation broth of step 6 may be a treatment solution that has passed through steps of step 2 and/or step 3.
- the fermentation broth of step 6 may be a treatment solution that has passed through at least one of steps 4, 5, 7, and 8 after passing through steps of step 2 and/or step 3.
- the largest impurity in the fermentation broth in which glycerol and alcohol are reduced is the cation of the pH adjusting agent introduced for pH control in the step of preparing the fermentation broth.
- the types of the cations can be various, and generally cations such as calcium and magnesium, but are not limited thereto. These cations, which exist in the form of various 3-HP salts through weak chemical bonds with 3-HP, can be efficiently removed in the form of precipitates through acid treatment.
- a filter press, drum filter, etc. may be used, but is not limited thereto, and any general method capable of removing the precipitate may be used.
- the pH of the solution can be reduced to about 1 to 3.
- the pH may be reduced to about 1.5 to about 2.5, for example, the pH may be reduced to about 1.5 to 2.0.
- Process 7 reducing ionic components in fermentation broth (electrodialysis and ion exchange)
- a method for obtaining the compound of the present invention may include reducing the ionic component in the fermentation broth.
- the fermentation broth of step 7 may be a treatment solution that has passed through steps of step 2 and/or step 3.
- the fermentation broth of step 7 may be a treatment solution that has undergone one or more steps of steps 4 to 6 or 8 after passing through steps of step 2 and/or step 3.
- a small amount of ions remaining after being removed in step 6 may be further removed in step 7.
- processes such as electrodialysis, ion exchange, and SMB chromatography can be applied to separate and reduce ionic components remaining in the fermentation broth.
- the ion may be a sulfate ion, a phosphate ion, a sodium ion, an ammonium ion, a calcium ion, a potassium ion, or a magnesium ion.
- the ionic component is, for example, about 20,000 ppm or less, such as about 19,000 ppm or less, such as about 18,500 ppm or less, such as about 18,000 ppm or less, such as about 17,500 ppm or less, such as about 17,000 ppm or less, such as about 16,000 ppm or less, such as about 100 to about 100 ppm 15,500 ppm, such as about 150 to 15,000 ppm.
- the concentration of the reduced ionic component may be, for example, greater than 0 ppm, such as greater than 10 ppm, such as greater than 20 ppm, such as greater than 50 ppm.
- Process 8 Step of increasing 3-HP concentration in fermentation broth
- the method for obtaining the compound of the present invention may include increasing the concentration of 3-HP in the fermentation broth in which the ionic component is reduced.
- the fermentation broth of step 8 may be a treatment solution that has passed through steps of step 2 and/or step 3.
- the fermentation broth of step 8 may be a treatment solution that has been subjected to one or more steps of steps 4 to 7 after passing through steps of step 2 and/or step 3.
- the concentration of 3-HP may be increased in the treatment solution having reduced ionic components by using methods such as evaporation and concentration.
- the concentration of 3-HP may be increased by evaporating and/or concentrating the fermentation broth from which components other than 3-HP are removed or the concentration is reduced.
- the concentration of 3-HP may be increased by performing step 8 after steps 1 to 7, and in this case, the concentrated fermentation broth is in the form of an aqueous solution in which almost all impurities except water are removed, that is, 3-HP may be a solution.
- the concentration of 3-HP in the concentrated fermentation broth in the form of an aqueous solution is, for example, 15 wt% or more, such as 16 wt% or more, such as 17 wt% or more, such as 18 wt% or more, such as 19 wt% or more, such as 20 wt% or more % or more.
- the concentration of 3-HP in the concentrated fermentation broth in the form of an aqueous solution may be about 80 wt% or less.
- evaporation and concentration may be performed by applying vacuum and/or heat, and the concentration of 3-HP may be adjusted by evaporating and removing water.
- the step of increasing the concentration of 3-HP using vacuum distillation is, for example, about 20 mbar or less, such as about 25 mbar or less, such as about 30 mbar or less, such as about 50 mbar or less, such as about 70 mbar or less, such as about 80 mbar or less It can be performed below mbar.
- the step of increasing the concentration of 3-HP using vacuum distillation is, for example, about 300 mbar or less, such as about 280 mbar or less, such as about 250 mbar or less, such as about 200 mbar or less, such as about 190 mbar or less, such as It can be performed below about 180 mbar.
- the distillation may be performed using a falling film distillation device, a wiper type thin film evaporation device, a thin film evaporation device, a centrifugal molecular distillation device, a thin film rising evaporation device, etc., but is not limited thereto.
- thermal recompression and mechanical recompression processes can be applied.
- the method for obtaining the compound of the present invention may further include recovering 3-HP from the fermentation broth.
- the fermentation broth of step 9 may be a treatment solution that has undergone one or more steps of steps 4 to 8 after passing through steps of step 2 and/or step 3.
- 3-HP can be recovered in aqueous solution.
- the method for obtaining the compound of the present invention can carry out all of the steps described above, can be carried out by selecting two or more steps, and can be carried out by selecting three or more steps. Further, the present invention may be practiced in any order with any selection of steps described herein. For example, the pH concentration in the fermentation broth may be increased after filtration, and filtration may be performed after increasing the pH concentration in the fermentation broth. In addition, the present invention may be carried out by adding other steps other than those described herein.
- a 3-HP fermentation broth was prepared through batch fermentation in a medium using glycerol as a sole carbon source using recombinant E. coli.
- it contained 100 g/L of 3-HP, 0.5 g/L of 1,3-PDO, and 0.3 g/L of acetic acid, and less than 0.1 g/L of glycerol. existed.
- the fermentation broth was filtered through a porous polymer membrane to separate insoluble matter. As a result, it was possible to recover 91% of 3-HP (the amount of 3-HP in the filtered fermentation broth compared to the amount of 3-HP in the fermentation broth added before filtration) compared to the initial fermentation broth put into the membrane.
- DI-WATER deionized water
- the filtered fermentation broth prepared in Experimental Example 1 was concentrated to prepare about 30 w/w% 3-HP solution, which was used as Feed in Experimental Example 2.
- the Feed contained 3-HP in the form of a calcium salt.
- a 380ml glass column was filled with cation exchange resin, and 20ml of 30% 3-HP fermentation solution was pulsed with a metering pump, and DI-Water was used as an eluent to pass through the ion exchange resin column from bottom to top at 10 ml/min. .
- Samples of 10 ml each of the liquid passing through the column were taken and analyzed by liquid chromatography (single column chromatography at 50 °C and space velocity of 1 hr -1 ).
- the filtered fermentation broth prepared in Experimental Example 1 was subjected to a concentration process to make about 20 w/v% 3-HP solution and used as Feed for Experimental Example 3.
- the Ca ion concentration was about 40,000ppm
- the concentration of 3-HP in the Feed was 213 g/L.
- the progress of the precipitation reaction was confirmed by monitoring pH and electrical conductivity. After the precipitation process, the concentration of Ca ions in the filtrate was confirmed to be 500 ppm or less (FIG. 4).
- the filtered fermentation broth made in Experimental Example 1 was used as Feed for Experimental Example 5 through the same treatment as in Experimental Example 3.
- the ion content in the Feed was about 16,600 ppm. Since the concentration of the ion to be treated is 3000 ppm or more, it is preferable to remove the main ion component by applying electrodialysis or SMB chromatography to efficiently remove the ion component. Ionic components in the fermentation broth may be removed using only one process among electrodialysis, ion exchange, and SMB chromatography, but it is advantageous in terms of reducing wastewater generation and operating costs to increase the efficiency of ion removal through a combination of two or more processes. it was expected
- the present invention relates to a method for obtaining a compound by removing at least a portion of insoluble substances or macromolecules from a fermentation broth and then performing one or more of the following steps (a) to (c), and recovering the desired compound:
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Abstract
Description
Claims (13)
- 발효액으로부터 불용성 물질 또는 거대분자의 적어도 일부를 제거한 후 하기 (a) 내지 (c) 중 하나 이상의 단계를 수행하고, 목적한 화합물을 회수하여 화합물을 수득하는 방법:(a) 발효액 내 목적한 화합물의 농도를 증가시키는 단계(b) 발효액 내 잔여 탄소원 또는 알코올의 농도를 감소시키는 단계;(c) 발효액 내 이온 성분의 농도를 감소시키는 단계.
- 제 1항에 있어서,상기 (a) 내지 (c) 중 하나 이상의 단계를 수행 시 임의의 단계를 2번 이상 반복하는 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 단계 (a)는 증발, 농축 및 증류로 구성되는 군으로부터 선택되는 하나 이상을 통하여 수행하는 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 단계 (c)는 하기 (c)' 또는 (c)''에 의하여 수행하는 것을 특징으로 하는 방법:(c)' : 발효액에 산 처리를 하여 이온 성분을 침전시킨 후 제거하는 공정(c)'' : 발효액을 전기투석, 이온교환 및 크로마토그래피로 구성되는 군으로부터 선택되는 하나 이상으로 처리하는 공정.
- 제 4항에 있어서,상기 (c)''의 크로마토그래피는 SMB(Simulated Moving Bed) 크로마토그래피인 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 불용성 물질은 세포를 포함하는 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 거대분자는 단백질, 다당류 또는 지질류인 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 목적한 화합물은 미생물 발효에 의하여 생성된 유기산인 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 (b)의 상기 탄소원은 글리세롤 또는 글루코스인 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 (b)의 상기 알코올은 미생물 발효에 의하여 생성된 알코올인 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 (b)의 상기 알코올은 1,3-프로판다이올인 것을 특징으로 하는 방법.
- 제 1항에 있어서,상기 단계 (b)는 발효액을 SMB(Simulated Moving Bed) 크로마토그래피에 적용하여 수행하는 것을 특징으로 하는 방법.
- 제 1항에 있어서,발효액으로부터 불용성 물질 또는 거대분자의 적어도 일부를 제거한 후 (a) 발효액 내 목적한 화합물의 농도를 증가시키고, (b) 발효액 내 잔여 탄소원 또는 알코올의 농도를 감소시키고, (c)' : 발효액에 산 처리를 하여 이온 성분을 침전시킨 후 제거한 후 (c)'' : 발효액을 전기투석, 이온교환 및 크로마토그래피로 구성되는 군으로부터 선택되는 하나 이상으로 처리하고, (a) 발효액 내 목적한 화합물의 농도를 증가시킨 후 목적한 화합물을 회수하여 화합물을 수득하는 것을 특징으로 하는 방법.
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JP2023577732A JP2024521504A (ja) | 2021-06-16 | 2022-06-16 | 発酵液から目的の化合物を得る方法 |
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Citations (6)
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KR100191357B1 (ko) * | 1997-02-03 | 1999-06-15 | 김효근 | 유기산의 회수방법 |
KR101294336B1 (ko) * | 2011-11-24 | 2013-08-08 | 대상 주식회사 | 젖산의 정제 방법 |
KR20150021065A (ko) * | 2012-05-23 | 2015-02-27 | 란자테크 뉴질랜드 리미티드 | 발효 및 모사 이동층 공정 |
KR20150127590A (ko) * | 2013-03-08 | 2015-11-17 | 질레코 인코포레이티드 | 바이오매스의 가공처리 |
KR20200051375A (ko) | 2018-11-05 | 2020-05-13 | 주식회사 엘지화학 | 아데노실트랜스퍼라제를 코딩하는 유전자로 형질전환된 미생물 및 이의 이용 |
KR20200088818A (ko) * | 2017-11-21 | 2020-07-23 | 젠와인 바이오테크놀로지 게엠바하 | 발효 배지로부터 시알산의 정제방법 |
-
2022
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- 2022-06-16 JP JP2023577732A patent/JP2024521504A/ja active Pending
- 2022-06-16 EP EP22825352.2A patent/EP4357331A1/en active Pending
- 2022-06-16 CN CN202280042529.2A patent/CN117500777A/zh active Pending
- 2022-06-16 WO PCT/KR2022/008552 patent/WO2022265429A1/ko active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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KR100191357B1 (ko) * | 1997-02-03 | 1999-06-15 | 김효근 | 유기산의 회수방법 |
KR101294336B1 (ko) * | 2011-11-24 | 2013-08-08 | 대상 주식회사 | 젖산의 정제 방법 |
KR20150021065A (ko) * | 2012-05-23 | 2015-02-27 | 란자테크 뉴질랜드 리미티드 | 발효 및 모사 이동층 공정 |
KR20150127590A (ko) * | 2013-03-08 | 2015-11-17 | 질레코 인코포레이티드 | 바이오매스의 가공처리 |
KR20200088818A (ko) * | 2017-11-21 | 2020-07-23 | 젠와인 바이오테크놀로지 게엠바하 | 발효 배지로부터 시알산의 정제방법 |
KR20200051375A (ko) | 2018-11-05 | 2020-05-13 | 주식회사 엘지화학 | 아데노실트랜스퍼라제를 코딩하는 유전자로 형질전환된 미생물 및 이의 이용 |
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JP2024521504A (ja) | 2024-05-31 |
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