CN106167814A - A kind of method improving acarbose fermentation unit - Google Patents
A kind of method improving acarbose fermentation unit Download PDFInfo
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- CN106167814A CN106167814A CN201610793405.4A CN201610793405A CN106167814A CN 106167814 A CN106167814 A CN 106167814A CN 201610793405 A CN201610793405 A CN 201610793405A CN 106167814 A CN106167814 A CN 106167814A
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- actinoplanes
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- 238000000855 fermentation Methods 0.000 title claims abstract description 39
- 230000004151 fermentation Effects 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 21
- 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 17
- 229960002632 acarbose Drugs 0.000 title claims abstract description 17
- 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 17
- 238000005286 illumination Methods 0.000 claims abstract description 35
- 241000187712 Actinoplanes sp. Species 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 229920001817 Agar Polymers 0.000 claims description 3
- 239000001888 Peptone Substances 0.000 claims description 3
- 108010080698 Peptones Proteins 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 239000008272 agar Substances 0.000 claims description 3
- 235000019319 peptone Nutrition 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 239000001963 growth medium Substances 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 5
- 230000010355 oscillation Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011218 seed culture Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 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 description 1
- 241000187844 Actinoplanes Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 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 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 1
- 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 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012807 shake-flask culturing Methods 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 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
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The present invention relates to a kind of method improving acarbose fermentation unit, be controlled improving fermentation unit by actinoplanes Actinoplanes sp. slant strains is cultivated illumination condition.During can be seen that Actinoplanes sp. slant culture according to experimental result, use electric filament lamp is light source, light application time control 12 20h/ days, illumination 120 180lux time can improve fermentation unit, especially illumination control the time 12 16h/ days, intensity of illumination be 150 180lux time fermentation unit significantly improve.
Description
Technical field
The present invention relates to a kind of method improving fermentation unit, particularly relate to a kind of side improving acarbose fermentation unit
Method, belongs to pharmaceutical technology field.
Background technology
Acarbose is by false four sugar substances of actinoplanes (Actinoplanessp) fermenting and producing, and Chinese is not
Double deoxidation-4 [[(1S, 4R, 5S, 6S) 4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexene] the amino]-(-D-of name: O-4,6-
Glycopyranosyl (1 → 4)-O-)-D-glycopyranosyl (1 → 4)-D-Glucopyranose..Acarbose energy and alpha-glucosidase
There is competitive inhibition (Wehmeier UF, Piepersberg W.Biotechology and molecular
Biology of the α-glucisidase inhibitoracarbose [J] .Appl Microbiol Biotechnol,
2004,63:613-625) suppress many sugar decomposition of food, make the absorption of sugar slow down accordingly, thus reduce postprandial hyperglycemia, coordinate
Diet Therapy diabetes.
The metabolic pathway of microorganism is that the metabolic pathway associated by many has been worked in coordination with, and its metabolic activity energy according to
The change of external environment carry out altitude mixture control (see Chu Ju, Li Yourong. modern industry fermentation control [M]. Beijing: chemistry work
Industry publishing house, 2002).The physiological property of strain is key factor for the generation of purpose product, but fermentation condition, such as substrate
Composition and metabolite and concentration thereof, temperature, pH value, the control of dissolved oxygen are not only related to the growth of microorganism, but also shadow
Ring the yield of metabolite.In sweat, composition and the condition of culture of culture medium are the biggest to yield effect, it is necessary to carry out optimum
Change and control.(see Luo Lixin. fermentable physiology [M]. Beijing: Chemical Industry Press, 2009).
Existing fermentation technology uses in strain access slant medium and carries out slant culture.During tradition slant culture
The omnidistance lucifuge of general employing or natural lighting, duration and intensity to illumination are not controlled, and there is the problems such as fermentation unit is low.
Summary of the invention
The purpose of the present invention is exactly to overcome the defect of prior art, provide a kind of side improving acarbose fermentation unit
Method, the method improves slant strains by light irradiation time, intensity of illumination and the lighting color during control slant culture
Quality, thus improve fermentation unit.
Of the present invention technical problem is that is solved by techniques below scheme.
A kind of method improving acarbose fermentation unit, by actinoplanes Actinoplanes sp. inclined-plane bacterium
Plant cultivation illumination condition and be controlled improving the method for fermentation unit.
The method of above-mentioned raising acarbose fermentation unit, described illumination condition controls to refer to that using electric filament lamp is light source,
Intensity of illumination is adjusted to 30-300lux, light application time controlled at 0-24 hour/day.
The method of above-mentioned raising acarbose fermentation unit, intensity of illumination is 120-180lux, it is furthermore preferred that intensity of illumination
For 150-180lux.
The method of above-mentioned raising acarbose fermentation unit, the illumination control time was at 12-20h/ days, it is furthermore preferred that illumination
The control time was at 12-16h/ days.
The method of above-mentioned raising acarbose fermentation unit, the cultivation of described slant strains, consisting of of its slant medium
Sucrose 30g/L, peptone 5g/L, KC10.5g/L, KH2P041.0g/L, TYR 1g/L, MgS040.5g/L, agar 20g/
L, solvent are water, and initial pH is 7.0.
The present invention, in R&D process, has been surprisingly found that illumination is to actinoplanes Actinoplanes sp. slant strains
Impact is relatively big, and the light note in adjustable inclined surface apparatus incubation produces impact to fermentation unit.Can be seen that according to experimental result
During Actinoplanes sp. slant culture, use electric filament lamp is light source, and light application time controls 12-20h/ days, illumination
Can improve fermentation unit during 120-180lux, especially illumination control the time 12-16h/ days, intensity of illumination be 150-180lux
Time fermentation unit significantly improve.
Accompanying drawing explanation
Fig. 1 is light irradiation time and the illumination influence curve figure to lab scale fermentation shake flask unit.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is described in further detail.
Embodiment 1 illumination condition is tested
(1) seed bottle seed culture
Every cultured fresh inclined plane inoculating in the 500m1 triangular flask that seed culture medium loading amount is 20%, 27 DEG C of temperature
Under the conditions of degree, on shaking table, 48h is cultivated in the speed oscillation with 250r/min, prepares shake-flask seed liquid；
(2) shake flask fermentation
By 15% inoculum concentration, cultured female bottle seed liquor is connected to the 500m1 triangular flask that fermentation medium loading amount is 10%
In, under 27 DEG C of temperature conditionss, 168h is cultivated in the speed oscillation with 250r/min；
Experimental result is shown in Fig. 1, as seen from Figure 1 during Actinoplanes sp. slant culture, uses electric filament lamp
For light source, light application time controls 12-20h/ days, illumination 120-180lux, more preferably 12-16h/ days, illumination 150-180lux.
Embodiment 2 contrast experiment
Preparation slant medium, its culture medium composition as follows: sucrose 30g/L, peptone 5g/L, KC10.5g/L,
KH2P041.0g/L, TYR 1g/L, MgS040.5g/L, agar 20g/L, solvent are water, and initial pH is 7.0.121 DEG C go out
Bacterium 30 minutes.
Preparation seed bottle culture medium, its culture medium composition is as follows: starch 10g/L, soybean cake powder 10g/L, CaCO32g/L、
Glycerol 20g/L, solvent are water, and initial pH is 7.0.121 DEG C of sterilizings 30 minutes.
Preparation fermentation shake flask culture medium, its culture medium composition is as follows: maltose 60g/L, glucose 20g/L, soybean cake powder
15g/L、FeCl30.2g/L、CaCL2 2g/L、CaCO34g/L, sodium glutamate 2g/L, KH2P04 1g/L, solvent are that water is initial
PH is 7.0.121 DEG C of sterilizings 30 minutes.
Prepared by slant strains: aseptic transfer low temperature glycerol pipe bacterial strain is in slant medium fresh, aseptic.One group of (comparison
Group 1) at 28 DEG C shading cultivate 6 days.At second group (matched group 2) 28 DEG C, Indoor Natural illumination (illumination 80-150lux) cultivates 6
My god.The incandescent light using 150lux at 3rd group (experimental group 1) 28 DEG C irradiates 16h/ days, cultivates 6 days.4th group of (experimental group
2) incandescent light using 180lux at 28 DEG C irradiates 12h/ days, cultivates 6 days.
Two groups of slant strains of picking are inoculated in seed culture medium respectively, under 27 DEG C of temperature conditionss, with 250r/ on shaking table
48h is cultivated in the speed oscillation of min, prepares shake-flask seed liquid；By 15% inoculum concentration, cultured female bottle seed liquor is connected to fermentation
Culture medium loading amount is in the 500m1 triangular flask of 10%, and under 27 DEG C of temperature conditionss, 168h is cultivated in the speed oscillation with 250r/min.Survey
Determine fermentation unit and the results are shown in Table 1.
Table 1 fermentation unit measurement result
As seen from the results in Table 1, by regulating the illumination condition of actinoplanes Actinoplanes sp. slant culture, energy
Fermentation unit is had a huge impact.Use electric filament lamp is light source, and light application time controls 12-20h/ days, illumination 120-
During 180lux, compared with using Indoor Natural illumination condition, it is possible to increase fermentation unit, especially illumination controls the time at 12-
16h/ days, intensity of illumination is when being 150-180lux, fermentation unit improves the most notable.
Claims (5)
1. the method improving acarbose fermentation unit, it is characterised in that by actinoplanes Actinoplanes
Sp. slant strains is cultivated illumination condition and is controlled improving the method for fermentation unit.
The method of raising acarbose fermentation unit the most according to claim 1, it is characterised in that described illumination condition control
System refers to that using electric filament lamp is light source, is adjusted to 30-300lux, light application time controlled at 0-24 hour/day by intensity of illumination.
The method of raising acarbose fermentation unit the most according to claim 2, it is characterised in that described intensity of illumination is
120-180lux, illumination controlled the time at 12-20h/ days.
The method of raising acarbose fermentation unit the most according to claim 3, it is characterised in that when described illumination controls
Between at 12-16h/ days, intensity of illumination is 150-180lux..
The method of raising acarbose fermentation unit the most according to claim 4, it is characterised in that described slant strains is trained
Support, its slant medium consist of sucrose 30g/L, peptone 5g/L, KC10.5g/L, KH2P041.0g/L, TYR
1g/L, MgS040.5g/L, agar 20g/L, solvent are water, and initial pH is 7.0.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610793405.4A CN106167814B (en) | 2016-08-31 | 2016-08-31 | A method of improving acarbose fermentation unit |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610793405.4A CN106167814B (en) | 2016-08-31 | 2016-08-31 | A method of improving acarbose fermentation unit |
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| Publication Number | Publication Date |
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| CN106167814A true CN106167814A (en) | 2016-11-30 |
| CN106167814B CN106167814B (en) | 2019-08-09 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115161365A (en) * | 2022-09-08 | 2022-10-11 | 上海现代制药股份有限公司 | Fermentation process for increasing acarbose yield |
| JP2022553183A (en) * | 2019-10-16 | 2022-12-22 | バイエル・アクチエンゲゼルシヤフト | Improved method of forming acarbose |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2282735A1 (en) * | 1997-02-28 | 1998-09-03 | Bayer Aktiengesellschaft | Acarbose (acb) cluster from actinoplanes sp. se 50/110 |
| CN101603066A (en) * | 2008-06-13 | 2009-12-16 | 上海医药工业研究院 | A kind of preparation method of acarbose |
| CN102140485A (en) * | 2010-12-25 | 2011-08-03 | 浙江工业大学 | Method for preparing acarbose through microbial fermentation |
| CN102978261A (en) * | 2012-08-24 | 2013-03-20 | 河北华荣制药有限公司 | High malt syrup and method for improving acarbose fermentation unit by using high malt syrup |
-
2016
- 2016-08-31 CN CN201610793405.4A patent/CN106167814B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2282735A1 (en) * | 1997-02-28 | 1998-09-03 | Bayer Aktiengesellschaft | Acarbose (acb) cluster from actinoplanes sp. se 50/110 |
| CN101603066A (en) * | 2008-06-13 | 2009-12-16 | 上海医药工业研究院 | A kind of preparation method of acarbose |
| CN102140485A (en) * | 2010-12-25 | 2011-08-03 | 浙江工业大学 | Method for preparing acarbose through microbial fermentation |
| CN102978261A (en) * | 2012-08-24 | 2013-03-20 | 河北华荣制药有限公司 | High malt syrup and method for improving acarbose fermentation unit by using high malt syrup |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022553183A (en) * | 2019-10-16 | 2022-12-22 | バイエル・アクチエンゲゼルシヤフト | Improved method of forming acarbose |
| JP7711052B2 (en) | 2019-10-16 | 2025-07-22 | バイエル・アクチエンゲゼルシヤフト | Improved method for forming acarbose |
| CN115161365A (en) * | 2022-09-08 | 2022-10-11 | 上海现代制药股份有限公司 | Fermentation process for increasing acarbose yield |
| CN115161365B (en) * | 2022-09-08 | 2023-01-06 | 上海现代制药股份有限公司 | A fermentation process for increasing the yield of acarbose |
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