CN113968794A - Process method for separating and purifying glutamine - Google Patents
Process method for separating and purifying glutamine Download PDFInfo
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- CN113968794A CN113968794A CN202111467920.0A CN202111467920A CN113968794A CN 113968794 A CN113968794 A CN 113968794A CN 202111467920 A CN202111467920 A CN 202111467920A CN 113968794 A CN113968794 A CN 113968794A
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- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims abstract description 41
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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 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a process for separating and extracting L-glutamine from fermentation liquor, which comprises the following steps: performing ceramic filtration and microfiltration, decoloring, adding a reagent I, concentrating, crystallizing, washing crystals, drying and the like. Wherein the reagent I is at least one selected from 3-acetylpyridine, (2,2,6, 6-tetramethyl-4-piperidyl) -1, 3-benzene diamide, 2, 6-di-tert-butylpyridine and N-methyl-N-vinyl acetamide. The reagent I increases the thermal stability, acid and alkali resistance of L-glutamine; impurities are not easy to separate out, and the product yield is greatly improved; meanwhile, the dosage of the reagent I is ppm level, and the reagent I cannot remain in the product. The process does not use ion exchange step, saves acid and alkali, and reduces waste water and waste liquid. The product purity is more than 99.0 percent, and the product yield is more than 90 percent. Has good industrial application prospect.
Description
Technical Field
The invention relates to the field of biochemical engineering, and particularly relates to a technological method for separating and extracting glutamine.
Background
L-glutamine (L-Gln) is an amino acid formed by amidation of gamma-carboxyl of L-glutamic acid, and has a chemical name of 2, 5-diamino-5-oxopentanoic acid, a relative molecular mass of 146.15, and a molecular formula: C5H10N2O3, is one of the essential amino acids constituting a protein. Glutamine is a white orthorhombic crystal or crystalline powder; has no odor and slight sweet taste, melts and decomposes at about 185 deg.C, is stable in crystalline state, is soluble in water, and is insoluble in organic solvents such as methanol, ethanol, acetone, and ethyl acetate. The isoelectric point was 5.65.
Besides being involved in protein synthesis, glutamine can be used as a nitrogen source to participate in synthesis of nucleic acid, glycoprotein and the like, and has close relation with tissue growth and repair. Medical research shows that human glutamine deficiency can cause various diseases, and the supplement of glutamine has wide and important influence on various functions of human bodies. Glutamine has a variety of functions such as enhancing immune function, maintaining acid-base balance, increasing cell volume, enhancing muscle cell protein synthesis, and the like. The application of glutamine in the medical field mainly comprises the following aspects: (1) for the treatment of motor syndrome and high labor or post-exercise fatigue recovery; (2) rebuilding immune system (for treating and recovering burn, AIDS, arthritis, etc.); (3) treating liver diseases and restoring liver function; (4) reducing the side effects of chemotherapy and radiotherapy in the treatment of cancer; (5) treating abdominal ulcer, Crohn's disease, allergic enteritis, ulcer, etc.; (6) can be widely used for maintaining brain function and treating mental retardation, epilepsy, Parkinson's syndrome, muscular atrophy and alcoholism.
At present, there are three major processes for glutamine production, namely chemical synthesis, fermentation and enzymatic conversion. Wherein the fermentation method is the main method for industrially producing glutamine at present. The ion exchange method is the main method for separation and purification. Since impurities such as bacteria, glutamic acid, proteins, saccharides, and inorganic salts are present in the fermentation liquid, the fermentation liquid is usually pretreated (filtration, centrifugation, etc.), pH is adjusted, separation is performed by anion and cation exchange resin column, and the effluent is concentrated and crystallized to obtain glutamine crystals. However, the ion exchange method has the disadvantages of large resin consumption, high acid and alkali consumption, and unstable L-glutamine due to heat and acid and alkali. The glutamic acid is decomposed under strong acid condition, and the yield is greatly reduced. In addition, the ion exchange method acid-base waste liquid is easy to cause environmental pollution. Therefore, researchers have proposed methods such as ultrafiltration, flocculation, electrodialysis, and combinations thereof in terms of pretreatment. In addition to the ion exchange method, the use of nanofiltration membranes for separation is the focus of current research. Mainly utilizes sieving effect and Donnan effect between ions and charged membrane. The nanofiltration membrane process does not have acid-base wastewater, but is relatively costly and has certain difficulties in its scale-up in view of technical problems. Therefore, there is a need in the art for a new technology to solve the problems in the extraction process of L-glutamine.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a process method for separating and extracting L-glutamine from fermentation liquor. The method does not use ion exchange step, thereby saving acid and alkali; greatly reducing the discharge of waste water and waste liquid. In the separation process, a specific reagent is added, so that the stability of the L-glutamine is improved, and the product yield is improved.
The invention provides a process for separating and extracting L-glutamine from fermentation liquor, which comprises the following steps: micro-filtering, decolorizing, adding reagent I to obtain mixed solution; concentrating, crystallizing, washing crystal, drying and the like. The reagent I is at least one selected from 3-acetylpyridine, (2,2,6, 6-tetramethyl-4-piperidyl) -1, 3-benzene diamide, 2, 6-di-tert-butylpyridine and N-methyl-N-vinyl acetamide.
Further, the concentration of the reagent I in the mixed solution is 10-1000 ppm; more preferably, the concentration of the reagent I in the mixed solution is 150-250 ppm. Further, after the step of adding the reagent I, the pH value of the solution is adjusted to 5.2-6.0; more preferably the pH is 5.65. The pH-adjusting acid is hydrochloric acid, phosphoric acid, sulfuric acid or nitric acid, preferably hydrochloric acid or sulfuric acid, and most preferably hydrochloric acid.
Further, the microfiltration step comprises: and (4) filtering the fermentation liquor with the pH value adjusted to 6.5-7.5 by using a filter membrane, and collecting the filtrate.
Further, in the microfiltration step, a filter membrane with the pore diameter of 0.2-0.5 μm is used for filtering the fermentation liquor, and the preferred filter membrane is at least one of a ceramic membrane, a glass membrane, a polytetrafluoroethylene membrane and a mixed cellulose membrane; the most preferred pore size is 0.3 μm to 0.45. mu.m.
Further, the temperature of the microfiltration step is 15-30 ℃, and the pressure is 1.5-2.0 MPa.
Further, the decoloring step includes: adding a decolorizing agent accounting for 0.02-2 wt% of the filtrate for impurity removal and decolorization, wherein the decolorizing agent is at least one of activated clay and powdered activated carbon; more preferably, the addition amount of the decoloring agent is 0.1-0.5 wt% of the mass of the filtrate.
Further, the vacuum concentration step includes: and (3) carrying out reduced pressure concentration on the mixed solution at the vacuum degree of-0.08 to-0.098 Mpa and the temperature of 50 to 75 ℃, and concentrating the mixed solution until the mass of the concentrated solution is 2.25 to 3.5 times of the solid content according to the solid content in the concentrated solution.
Further, the crystallizing step comprises: stirring and crystallizing for at least 2 hours at the temperature of 0-25 ℃, stirring at the speed of 50-200 rpm, and filtering; most preferably 3-5 ℃, stirring for crystallization for at least 2h, and stirring speed of 100-150 rpm.
Further, the crystal washing step comprises: adding 40-95% ethanol with the weight 1-4 times that of the filtered crystal, stirring and washing the crystal for at least 20min, and filtering; most preferably 95% ethanol filtration at 2 times the weight of the crystals.
Further, the vacuum drying step comprises: drying under the vacuum degree of-0.08 to-0.098 Mpa to obtain the L-glutamine with the purity of more than 99.0 percent.
Compared with the prior art, the invention has the following beneficial effects:
according to the technical scheme, the reagent I is added during concentration and crystallization, so that the thermal stability and the acid and alkali resistance of the L-glutamine are improved; glutamic acid impurities in the L-glutamine fermentation liquor are not easy to separate out, and the L-glutamine is easier to separate by concentration, so that the product yield is greatly improved; meanwhile, the influence of pH adjustment process and the like on the yield of the L-glutamine in the concentration and crystallization process is avoided; and the dosage of the reagent I is ppm level, and the reagent I can be directly washed clean by ethanol in the final crystal washing process and cannot remain in the product. The process provided by the invention does not use an ion exchange step, saves acid and alkali, and greatly reduces the discharge of waste water and waste liquid. The final product has high quality, the purity is more than 98.0 percent, and the product yield is more than 90 percent.
Detailed Description
The present invention is further illustrated by the following examples, but it should be understood that the scope of the present invention is not limited by the examples. In the present invention, percentages and percentages are by mass unless otherwise specifically indicated. Unless otherwise specified, the experimental methods used are conventional methods, and the materials, reagents and the like used are commercially available.
Example 1
Taking 1L of L-glutamine fermentation liquor, wherein the content of L-glutamine is 60.3 g. Filtering the fermentation liquor by a ceramic membrane with the aperture of 0.3 mu m, wherein the temperature of the system is 25 ℃, and the pressure is 1.5 MPa. Adding 0.5% active carbon into the micro-filtered clear liquid, stirring for decolorizing for 30min, and filtering. Adding 200ppm 3-acetylpyridine into the decolorized solution, stirring at room temperature for 30min, and mixing. Adjusting pH to 5.65 with hydrochloric acid, vacuum concentrating at-0.098 Mpa at 75 deg.C under reduced pressure until the solid content of decolorized solution is 2.5 times that of decolorized solution. Collecting the concentrated solution, and stirring for crystallization at the temperature of 4 ℃, wherein the stirring speed is 100 rpm; filtering, adding 2 times of 95% ethanol into the filtered crystal, washing the crystal for 30min, filtering, and vacuum drying to obtain 55.8g of L-glutamine with yield of 92.0% and purity of 99.7%.
Example 2
Taking 1L of L-glutamine fermentation liquor, wherein the content of L-glutamine is 60.3 g. Filtering the fermentation liquor by a ceramic membrane with the aperture of 0.3 mu m, wherein the temperature of the system is 25 ℃, and the pressure is 1.5 MPa. Adding 0.5% active carbon into the micro-filtered clear liquid, stirring for decolorizing for 30min, and filtering. Adding 100ppm 3-acetylpyridine into the decolorized solution, stirring at room temperature for 30min, and mixing. Adjusting pH to 5.65 with hydrochloric acid, vacuum concentrating at-0.098 Mpa at 75 deg.C under reduced pressure until the solid content of decolorized solution is 2.5 times that of decolorized solution. Collecting the concentrated solution, and stirring for crystallization at the temperature of 4 ℃, wherein the stirring speed is 100 rpm; filtering, adding 2 times of 95% ethanol into the filtered crystal, washing the crystal for 30min, filtering, and vacuum drying to obtain 50.5g of L-glutamine with yield of 82.1% and purity of 98.1%.
Example 3
Taking 1L of L-glutamine fermentation liquor, wherein the content of L-glutamine is 60.3 g. Filtering the fermentation liquor by a ceramic membrane with the aperture of 0.3 mu m, wherein the temperature of the system is 25 ℃, and the pressure is 1.5 MPa. Adding 0.5% active carbon into the micro-filtered clear liquid, stirring for decolorizing for 30min, and filtering. Adding 500ppm 3-acetylpyridine into the decolorized solution, stirring at room temperature for 30min, and mixing. Adjusting pH to 5.65 with hydrochloric acid, vacuum concentrating at-0.098 Mpa at 75 deg.C under reduced pressure until the solid content of decolorized solution is 2.5 times that of decolorized solution. Collecting the concentrated solution, and stirring for crystallization at the temperature of 4 ℃, wherein the stirring speed is 100 rpm; filtering, adding 2 times of 95% ethanol into the filtered crystal, washing the crystal for 30min, filtering, and vacuum drying to obtain 54.0g of L-glutamine with yield of 89.0% and purity of 99.4%.
Example 4
Taking 1L of L-glutamine fermentation liquor, wherein the content of L-glutamine is 60.3 g. Filtering the fermentation liquor by a ceramic membrane with the aperture of 0.3 mu m, wherein the temperature of the system is 25 ℃, and the pressure is 1.5 MPa. Adding 0.5% active carbon into the micro-filtered clear liquid, stirring for decolorizing for 30min, and filtering. Adding 200ppm 3-acetylpyridine into the decolorized solution, stirring at room temperature for 30min, and mixing. Adjusting pH to 5.65 with hydrochloric acid, vacuum concentrating at-0.098 Mpa at 75 deg.C under reduced pressure until the solid content of decolorized solution is 2.5 times that of decolorized solution. Collecting the concentrated solution, and stirring for crystallization at the temperature of 4 ℃, wherein the stirring speed is 100 rpm; filtering, adding 2 times of 40% ethanol into the filtered crystal, washing the crystal for 30min, filtering, and vacuum drying to obtain 51g of L-glutamine with yield of 94.1% and purity of 99.4%.
Comparative example 1
The process route of the patent CN106434781B embodiment: fermentation liquor, microfiltration, flocculation, isoelectric point sedimentation, secondary flocculation, clear liquid concentration and isoelectric point crystallization; as a result: the yield was 88.6% and the purity was 99.1%.
The process route of the embodiment of patent CN 104745666B: fermentation liquor-microfiltration-primary crystallization-redissolution, strong acid cation exchange, weak base anion exchange, weak acid cation exchange-activated carbon decolorization-single-effect low-temperature concentration-crystallization at 5 ℃ for 10 hours; as a result: the yield was 67%, and the purity was 98%.
The process route of the patent CN102924321B embodiment: fermentation liquor, microfiltration, concentration, crystallization at 7 ℃ for 10h to 0.5 time, washing, redissolution, cation and anion exchange, nanofiltration, decoloration, secondary crystallization for 10 ℃ and 10h, and the results are that: the yield thereof was found to be 64% and the purity thereof was found to be 99.1%.
Comparative example 2
Three groups of L-glutamine fermentation liquor are taken for parallel experiments, each group is 1L, and the L-glutamine content is 61.7g, 63.1g and 60.3g respectively. The fermentation liquor is filtered by ceramic membranes with the aperture of 0.3 mu m respectively, the temperature of the system is 25 ℃, and the pressure is 1.5 MPa. Adding 0.5% active carbon into the micro-filtered clear liquid, stirring for decolorizing for 30min, and filtering. Reagent I is not added into the three groups of decolored liquid. Stirring at room temperature for 30min, and mixing. Adjusting pH to 5.65 with hydrochloric acid, vacuum concentrating at-0.098 Mpa at 75 deg.C under reduced pressure until the solid content of decolorized solution is 2.5 times that of decolorized solution. Collecting concentrated solution, and respectively stirring for crystallization at 4 ℃ at a stirring speed of 100 rpm; filtering respectively, adding 2 times of 95% ethanol into the filtered crystals to wash the crystals for 30min, filtering, and vacuum drying to obtain L-glutamine, weighing respectively, calculating the yields of 68.2%, 65.9% and 67.7%, respectively, and detecting to obtain the product with the purities of 93%, 95% and 97.0%.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and those skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. A process for separating and extracting L-glutamine from fermentation liquor is characterized by comprising the following steps: microfiltration, decoloring, adding a reagent I to obtain a mixed solution, concentrating and crystallizing; the reagent I is at least one selected from 3-acetylpyridine, (2,2,6, 6-tetramethyl-4-piperidyl) -1, 3-benzene diamide, 2, 6-di-tert-butylpyridine and N-methyl-N-vinyl acetamide.
2. The process according to claim 1, wherein the concentration of the reagent I in the mixed solution is 10 to 1000 ppm.
3. The process as claimed in claim 1 or 2, wherein the concentration of the reagent I in the mixed solution is 150-250 ppm.
4. The process of claim 1, wherein the step of adding reagent I is further followed by adjusting the pH of the solution to 5.2 to 6.0.
5. The process of claim 1, wherein the microfiltration step comprises: adjusting the pH value of the fermentation liquor to 6.5-7.5, filtering the fermentation liquor by a filter membrane with the aperture of 0.2-0.5 mu m, and collecting filtrate.
6. The process of claim 5, wherein the filtration membrane is at least one selected from the group consisting of ceramic membrane, glass membrane, polytetrafluoroethylene membrane, and mixed cellulose membrane.
7. The process according to claim 1, characterized in that said decolorization step comprises: and adding a decolorizing agent accounting for 0.02-2 wt% of the filtrate for impurity removal and decolorization, wherein the decolorizing agent is selected from activated clay and/or powdered activated carbon.
8. The process according to claim 7, wherein the decolorizing agent is added in an amount of 0.1 to 0.5 wt% based on the mass of the filtrate.
9. The process according to claim 1, wherein the step of concentrating under reduced pressure comprises: and carrying out reduced pressure concentration on the mixed solution at the vacuum degree of-0.08 to-0.098 Mpa and the temperature of 50 to 75 ℃.
10. The process according to claim 1, wherein the crystallization step comprises: stirring and crystallizing for at least 2 hours at the temperature of 0-25 ℃, stirring at the speed of 50-200 rpm, and filtering.
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