CN112646850A - Method for improving acarbose fermentation yield - Google Patents
Method for improving acarbose fermentation yield Download PDFInfo
- Publication number
- CN112646850A CN112646850A CN202110105478.0A CN202110105478A CN112646850A CN 112646850 A CN112646850 A CN 112646850A CN 202110105478 A CN202110105478 A CN 202110105478A CN 112646850 A CN112646850 A CN 112646850A
- Authority
- CN
- China
- Prior art keywords
- fermentation
- tank
- volume
- acarbose
- culture
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 230000004151 fermentation Effects 0.000 title claims abstract description 96
- 238000000855 fermentation Methods 0.000 title claims abstract description 95
- 238000000034 method Methods 0.000 title claims abstract description 24
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 title claims abstract description 22
- 229960002632 acarbose Drugs 0.000 title claims abstract description 22
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 239000007788 liquid Substances 0.000 claims description 32
- 235000015097 nutrients Nutrition 0.000 claims description 30
- 239000000126 substance Substances 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 22
- 238000009423 ventilation Methods 0.000 claims description 17
- 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 15
- 238000007599 discharging Methods 0.000 claims description 15
- 239000008103 glucose Substances 0.000 claims description 15
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 14
- 244000068988 Glycine max Species 0.000 claims description 14
- 235000010469 Glycine max Nutrition 0.000 claims description 14
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 14
- 239000000843 powder Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000002609 medium Substances 0.000 claims description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- 239000001963 growth medium Substances 0.000 claims description 10
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 8
- 239000001110 calcium chloride Substances 0.000 claims description 8
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 claims description 7
- 229920002261 Corn starch Polymers 0.000 claims description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 6
- 239000008120 corn starch Substances 0.000 claims description 6
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 6
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 6
- 235000011187 glycerol Nutrition 0.000 claims description 6
- 238000010899 nucleation Methods 0.000 claims description 6
- 238000011218 seed culture Methods 0.000 claims description 6
- 238000005273 aeration Methods 0.000 claims description 3
- 230000000813 microbial effect Effects 0.000 abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 238000005286 illumination Methods 0.000 description 5
- 230000001502 supplementing effect Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 241000187712 Actinoplanes sp. Species 0.000 description 3
- 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 description 3
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000009655 industrial fermentation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000005514 two-phase flow Effects 0.000 description 1
Classifications
-
- 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
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
-
- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention relates to a method for improving fermentation yield of acarbose, and particularly belongs to the technical field of microbial fermentation.
Description
Technical Field
The invention relates to the field of microbial fermentation, in particular to a method for improving acarbose fermentation yield.
Background
Acarbose is a secondary metabolite produced by Actinoplanes sp. Because the compound has the activity of inhibiting Q-glucosidase, can reduce the decomposition of polysaccharide and oligosaccharide in human intestinal tracts, and further reduce the blood sugar concentration, the compound is clinically used as a medicament for treating diabetes.
Acarbose is commonly produced using industrial fermentation processes. The metabolic pathways of acarbose microorganisms are synergistically completed by many associated metabolic pathways, and the metabolic activities thereof can be highly regulated according to changes in the external environment (see stock torch, Liyong, modern Industrial fermentation control [ M ]. Beijing: chemical industry Press, 2002). The fermentation conditions, such as the substrate component, the metabolite, the concentration, the pH value and the dissolved oxygen, are controlled to not only relate to the growth of the microorganism, but also influence the yield of the metabolite. During the fermentation process, the composition of the culture medium and the culture conditions greatly affect the yield, and the optimal control is required. (see Roxisin. microbial fermentation physiology [ M ]. Beijing: chemical industry Press, 2009).
CN110541017A discloses a method for increasing the production of acarbose, which is realized by the following steps: the concentrations of glucose and maltose were monitored during the fermentation, and when they became low, glucose solution and maltose solution were continuously fed to control the concentration ratio of glucose and maltose to 1:4 in the fermentor culture.
CN110564794A discloses a fermentation method of acarbose, which is realized by the following methods: when the concentration of the glucose in the fermentation liquor is reduced to 3-10 g/L, feeding a glucose solution, so that the content of the glucose in the fermentation liquor is controlled to be 3-10 g/L; and when the volume concentration of the thalli in the fermentation liquor reaches 25-30%, adding the maltose syrup solution for 4-5 times, wherein the maltose syrup concentration in the fermentation liquor is increased by 10-30 g/L each time.
CN106167814A discloses a method for improving acarbose fermentation units, which is realized by the following steps: the fermentation unit is improved by controlling the illumination condition for culturing Actinoplanes sp. According to the experimental result, in the process of Actinoplanes sp. slant culture, an incandescent lamp is used as a light source, the fermentation unit can be improved when the illumination time is controlled to be 12-20 h/day and the illumination intensity is 120-180lux, and particularly the fermentation unit is obviously improved when the illumination control time is 12-16 h/day and the illumination intensity is 150-180 lux.
The prior art improves the yield by supplementing glucose and maltose syrup and illuminating, and researches and creates the method for seeking more methods for improving the fermentation yield of acarbose.
Disclosure of Invention
The invention aims to provide a method capable of effectively improving the fermentation yield of acarbose.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for increasing the fermentation yield of acarbose comprises introducing gas, stirring, supplementing nutrients, and discharging a certain volume of liquid.
As some preferred embodiments of the invention, the nutrient comprises the following components: 60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, 2g/L, K g of sodium glutamate2HPO41g/L, solvent water, initial pH 7.0.
As some preferred embodiments of the invention, the nutrient is supplemented for 40h +/-2 hours from the fermentation culture, the nutrient supplementing speed is 40-200L/h, and the nutrient supplementing concentration is 1.5 times of the fermentation liquor.
As some preferred embodiments of the present invention, the discharge time of the feed liquid is 80-100h from the beginning of fermentation, and the discharge volume of the feed liquid is adjusted to maintain the fermentation liquid volume in the fermentation tank to 2/3 of the volume of the fermentation tank.
As some preferred embodiments of the invention, the method specifically comprises the following steps:
(1) the slant strain is subjected to ventilation stirring culture at 27-28 ℃ in a two-stage seeding tank to obtain a seed solution, wherein the seed culture medium comprises the following components: corn starch 15.0g/L, soybean cake powder 40.0g/L, glycerin 20.0g/L, K2HPO4 0.1g/L，CaCO32.0g/L, water as solvent, pH6.6-7.0;
(2) inoculating the seed solution into a fermentation medium in a proportion of 10-20%, performing fermentation culture at the temperature of 27-28 ℃ under the condition of ventilation and stirring, continuously feeding 40-200L/h of nutrient substances into the tank after 40h +/-2 h, wherein the concentration of the supplemented nutrient substances is 1.5 times of that of the fermentation liquid, and the fermentation medium and the nutrient substances comprise the following components:
60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, 2g/L, K g of sodium glutamate2HPO41g/L, water as solvent, and 7.0 of initial pH;
(3) the volume in the fermentation tank reaches 2/3 within 90h +/-2 h, batch discharging is carried out through a discharging pipeline, the volume of the liquid in the fermentation tank is maintained to be 2/3 of the volume of the fermentation tank, and the total fermentation culture lasts 140-180 h.
As some preferred embodiments of the invention, the tank pressure is 0.04 to 0.07MPa, the aeration ratio is 0.5 to 1.8vvm, and the stirring speed is 70 to 145 rpm.
As some preferred embodiments of the invention, the slant strain is inoculated in an amount of 0.1% of the volume of the medium in the seed tank.
In the present invention, it was found that the dissolved oxygen in the fermentation liquid in the tank has a close relationship with the partial pressure of oxygen in the air, the tank pressure, the surface area of the bubbles, the residence time of the bubbles, and the like. Compressed air is introduced into the tank, the stirring blades break bubbles to increase the surface area, and the liquid flow increases the residence time to increase the dissolved oxygen level of the liquid in the tank. And simulating gas-liquid two-phase flow in the fermentation tank according to working conditions by computing fluid mechanics software FLUENT, thereby obtaining a corresponding gas content cloud chart to explore the mass transfer mixing effect in the fermentation tank. The simulation shows that the dissolved oxygen condition of the upper layer of the fermentation tank is poor, which is not beneficial to the growth and metabolism of microorganisms. In order to avoid the phenomenon of local metabolism failure in the tank due to uneven distribution of dissolved oxygen, it is equally necessary to control the liquid level in the tank and supplement nutrients by intermittent discharge volume.
Adopt the produced beneficial effect of above-mentioned technical scheme to lie in:
the method of continuously supplementing nutrient substances and discharging the feed liquid stably maintains the feed liquid at a certain liquid level, and is matched with ventilation and stirring to maintain dissolved oxygen and nutrient substances in the feed liquid in a better range, promote the growth of the acarbose bacteria and the production of fermentation units, and further improve the acarbose fermentation yield. Experiments prove that the method provided by the invention can improve the yield by 10 percent by comparing the continuous feeding and discharging of the feed liquid with the simple feeding to maintain the fermentation yield with a certain volume.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in detail and fully with reference to the following embodiments.
Example 1
(1) The slant strain is subjected to ventilation stirring culture at 27 ℃ in a two-stage seeding tank to obtain a seed solution, wherein the seed culture medium comprises the following components: corn starch 15.0g/L, soybean cake powder 40.0g/L, glycerin 20.0g/L, K2HPO4 0.1g/L，CaCO32.0g/L, water as solvent, pH6.8.
(2) Inoculating 15% of seed liquid into a fermentation medium, performing fermentation culture at 28 ℃ under the condition of ventilation and stirring, wherein the tank pressure is 0.05MPa, the ventilation ratio is 1.1vvm, the stirring speed is 105rpm, nutrient substances are continuously supplemented into the tank at the speed of 200L/h after 40h, the concentration of the nutrient substances is 1.5 times that of the initial fermentation medium, and the nutrient substances and the fermentation medium consist of the following components:
60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, 2g/L, K g of sodium glutamate2HPO4I g/L, solvent is water, and initial pH is 7.0;
(3) and (3) when the volume of the tank reaches 40t after about 90h, discharging in batches through a discharging pipeline, maintaining the volume of the feed liquid at 40 +/-1 t, and performing total fermentation culture for 160 h.
Example 2
(1) The slant strain is subjected to ventilation stirring culture at 27 ℃ in a two-stage seeding tank to obtain a seed solution, wherein the seed culture medium comprises the following components: corn starch 15.0g/L, soybean cake powder 40.0g/L, glycerin 20.0g/L, K2HPO4 0.1g/L，CaCO32.0g/L, water as solvent, pH7.0;
(2) inoculating the seed liquid into a fermentation medium according to a proportion of 10%, performing fermentation culture at a temperature of 28 ℃ under the condition of ventilation and stirring, wherein the tank pressure is 0.07MPa, the ventilation ratio is 1.8vvm, the stirring speed is 70rpm, 150L/h of nutrient substances are continuously fed into the tank after 40h, the concentration of the supplemented nutrient substances is 1.5 times of that of the fermentation liquid, and the fermentation medium and the nutrient substances comprise the following components:
60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, 2g/L, K g of sodium glutamate2HPO41g/L, water as solvent, and 7.0 of initial pH;
(3) the volume of the fermentation tank reaches 2/3 within 90h, batch discharging is carried out through a discharging pipeline, the volume of the feed liquid in the fermentation tank is maintained to be 2/3 of the volume of the fermentation tank, and the total fermentation culture time is 150 h.
Example 3
(1) The slant strain is subjected to ventilation stirring culture at 28 ℃ in a two-stage seeding tank to obtain a seed solution, wherein the seed culture medium comprises the following components: corn starch 15.0g/L, soybean cake powder 40.0g/L, glycerin 20.0g/L, K2HPO4 0.1g/L，CaCO32.0g/L, water as solvent, pH7.0;
(2) inoculating the seed liquid into a fermentation medium in a proportion of 20%, performing fermentation culture at a temperature of 28 ℃ under the condition of ventilation and stirring, wherein the tank pressure is 0.04MPa, the ventilation ratio is 0.5vvm, the stirring speed is 145rpm, 80L/h of nutrient substances are continuously fed into the tank after 40h, the concentration of the supplemented nutrient substances is 1.5 times that of the fermentation liquid, and the fermentation medium and the nutrient substances comprise the following components:
60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, grain2g/L, K g of sodium amino acid2HPO41g/L, water as solvent, and 7.0 of initial pH;
(3) the volume of the fermentation tank reaches 2/3 within 90h, batch discharging is carried out through a discharging pipeline, the volume of the feed liquid in the fermentation tank is maintained to be 2/3 of the volume of the fermentation tank, and the total fermentation culture time is 170 h.
Comparative example 1
The strain is subjected to ventilation stirring culture at 27 ℃ in a two-stage seeding tank to obtain a seed solution, wherein the seed culture medium comprises the following components: corn starch 15.0g/L, soybean cake powder 40.0g/L, glycerin 20.0g/L, K2HPO4 0.1g/L，CaCO32.0g/L, water as solvent, pH6.8.
Inoculating the seed liquid into a fermentation culture medium according to a proportion of 15%, performing fermentation culture at a temperature of 28 ℃ under the condition of ventilation and stirring, wherein the pressure of a tank is 0.05MPa, the ventilation ratio is 1.1vvm, the stirring speed is 105rpm, nutrient substances are continuously supplemented into the tank at a speed of 200L/h after 40h, the concentration of the nutrient substances is 1.5 times of that of the initial fermentation culture medium, and the used nutrient substances and the fermentation culture medium consist of the following components:
60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, 2g/L, K g of sodium glutamate2HPO4I g/L, solvent is water, and initial pH is 7.0;
and stopping feeding when the volume of the tank reaches about 45t in about 120h, and performing total fermentation culture for 160h when the volume of the tank liquid is 45 +/-1 t.
Examples of effects
The cycle, level maintenance volume, fermentation units and fermentation yields for example 1 and comparative example 1 are reported in the following table:
| procedure (ii) | Period of time | Volume of | Unit of | Yield of the product |
| Example 1 | 160 | 40 | 6234 | 303.188 |
| Comparative example 1 | 160 | 45 | 6089 | 274.005 |
As can be seen from the above table, both the fermentation units and the fermentation yields of the tank batches of example 1 are superior to those of comparative example 1. The fermentation yield can be improved by about 10%.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (7)
1. A method for improving acarbose fermentation yield is characterized in that nutrient substances are supplemented by aeration and stirring in the fermentation process, and a certain volume of feed liquid is discharged at the same time.
2. The method for increasing acarbose fermentation yield according to claim 1, wherein the nutrients comprise the following components: 60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, 2g/L, K g of sodium glutamate2HPO41g/L, solvent water, initial pH 7.0.
3. The method for improving acarbose fermentation yield according to claim 1, wherein the nutrient is supplemented at a rate of 40-200L/h from the fermentation culture time of 40h ± 2h, and the concentration of the nutrient is 1.5 times that of the fermentation broth.
4. The method for improving the fermentation yield of acarbose according to claim 1, wherein the discharging time of the feed liquid is 80-100h from the beginning of the fermentation, and the discharging volume of the feed liquid is 2/3 which is the volume of the fermentation liquid in the fermentation tank.
5. The method for improving acarbose fermentation yield according to claim 1, which specifically comprises the following steps:
(1) the slant strain is subjected to ventilation stirring culture at 27-28 ℃ in a two-stage seeding tank to obtain a seed solution, wherein the seed culture medium comprises the following components: corn starch 15.0g/L, soybean cake powder 40.0g/L, glycerin 20.0g/L, K2HPO4 0.1g/L，CaCO32.0g/L, water as solvent, pH6.6-7.0;
(2) inoculating the seed solution into a fermentation medium in a proportion of 10-20%, performing fermentation culture at the temperature of 27-28 ℃ under the condition of ventilation and stirring, continuously feeding 40-200L/h of nutrient substances into the tank after 40h +/-2 h, wherein the concentration of the supplemented nutrient substances is 1.5 times of that of the fermentation liquid, and the fermentation medium and the nutrient substances comprise the following components:
60g/L of maltose, 20g/L of glucose and 15g/L, FeCl of soybean cake powder30.5 g/L, 2g/L, CaCO g of calcium chloride34 g/L, 2g/L, K g of sodium glutamate2HPO41g/L, water as solvent, and 7.0 of initial pH;
(3) the volume in the fermentation tank reaches 2/3 within 90h +/-2 h, batch discharging is carried out through a discharging pipeline, the volume of the liquid in the fermentation tank is maintained to be 2/3 of the volume of the fermentation tank, and the total fermentation culture lasts 140-180 h.
6. The method for improving the fermentation yield of acarbose according to claim 5, wherein in the step (2), the tank pressure is 0.04-0.07MPa, the aeration ratio is 0.5-1.8vvm, and the stirring speed is 70-145 rpm.
7. The method for increasing acarbose fermentation yield according to claim 1, wherein the slant strain is inoculated in an amount of 0.1% of the volume of the medium in the seed tank.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110105478.0A CN112646850A (en) | 2021-01-26 | 2021-01-26 | Method for improving acarbose fermentation yield |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110105478.0A CN112646850A (en) | 2021-01-26 | 2021-01-26 | Method for improving acarbose fermentation yield |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112646850A true CN112646850A (en) | 2021-04-13 |
Family
ID=75370868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110105478.0A Pending CN112646850A (en) | 2021-01-26 | 2021-01-26 | Method for improving acarbose fermentation yield |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112646850A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL121733A (en) * | 1996-09-13 | 2001-05-20 | Bayer Ag | Osmotically controlled fermentation process for the preparation of acarbose |
| CN102559813A (en) * | 2012-01-09 | 2012-07-11 | 杭州华东医药集团生物工程研究所有限公司 | Low-impurity acarbose and preparation method thereof |
| CN111850068A (en) * | 2020-06-18 | 2020-10-30 | 刘建阳 | Method for improving xanthan gum fermentation efficiency |
| CN112048532A (en) * | 2020-09-18 | 2020-12-08 | 山东鲁抗医药股份有限公司 | Method for producing acarbose by fermentation |
-
2021
- 2021-01-26 CN CN202110105478.0A patent/CN112646850A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL121733A (en) * | 1996-09-13 | 2001-05-20 | Bayer Ag | Osmotically controlled fermentation process for the preparation of acarbose |
| CN102559813A (en) * | 2012-01-09 | 2012-07-11 | 杭州华东医药集团生物工程研究所有限公司 | Low-impurity acarbose and preparation method thereof |
| CN111850068A (en) * | 2020-06-18 | 2020-10-30 | 刘建阳 | Method for improving xanthan gum fermentation efficiency |
| CN112048532A (en) * | 2020-09-18 | 2020-12-08 | 山东鲁抗医药股份有限公司 | Method for producing acarbose by fermentation |
Non-Patent Citations (1)
| Title |
|---|
| 黄芳一等: "《发酵工程》", 31 August 2019 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102533889B (en) | Method for continuously fermenting lysine | |
| CN103060393A (en) | Production and fermentation process for citric acid | |
| CN110846362B (en) | Neomycin sulfate fermentation clean production method | |
| CN110499345B (en) | Fermentation method of vitamin k2(MK-7 type) | |
| CN106929548B (en) | Process for producing malic acid by fermenting aspergillus oryzae | |
| CN110541014A (en) | method for producing tryptophan by using fed-batch culture solution through fermentation | |
| CN109182438B (en) | Production of vitamin B by fermentation of bacillus2Culture medium and culture method | |
| CN108719991B (en) | A method for preparing red rice containing Bacillus natto from bean dregs and bean curd yellow serofluid | |
| CN110205350A (en) | One kind improving vitamin B based on the regulation of ammonia nitrogen index12The method of yield | |
| CN108018324B (en) | Fermentation medium for producing doramectin and preparation method and application thereof | |
| CN110283854B (en) | Fermentation medium, application thereof and method for preparing lycopene by utilizing Blakeslea trispora fermentation | |
| CN113072599A (en) | Method for preparing natural hesperidin by biological fermentation and extraction | |
| CN112501221A (en) | Method for improving conversion rate of threonine and saccharic acid | |
| CN109576196B (en) | Fermentation medium for producing doramectin and production method of doramectin | |
| CN112646850A (en) | Method for improving acarbose fermentation yield | |
| CN115181684B (en) | MK-7 fermentation medium | |
| CN106591401B (en) | Fermentation promoter for increasing yield of gentamicin C1a and addition method thereof | |
| CN102533891A (en) | Production method of lysine | |
| CN110511974A (en) | A kind of fermentation process improving abomacetin fermentation potency | |
| CN105255954A (en) | Fermentation method for producing erythritol | |
| CN105586374B (en) | A method of sugar production doractin is mended based on metabolizing parameters reduced sugar | |
| CN111303248B (en) | Material supplementing method for improving teicoplanin fermentation yield | |
| CN108300742A (en) | A kind of method that current adding substrate enzyme prepares γ-aminobutyric acid | |
| CN109609567B (en) | Green production method of L-tryptophan by using mycoprotein enzymolysis liquid to replace yeast powder | |
| CN113755343A (en) | Fermentation medium for high yield of gibberellic acid and fermentation method for high yield of gibberellic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210413 |
|
| RJ01 | Rejection of invention patent application after publication |