CN108070623A - A kind of method for improving Pravastatin fermentation yield - Google Patents
A kind of method for improving Pravastatin fermentation yield Download PDFInfo
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- CN108070623A CN108070623A CN201610990905.7A CN201610990905A CN108070623A CN 108070623 A CN108070623 A CN 108070623A CN 201610990905 A CN201610990905 A CN 201610990905A CN 108070623 A CN108070623 A CN 108070623A
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Abstract
The present invention provides a kind of methods for improving Pravastatin fermentation yield, using Actinomycesa lmadurae as fermentation strain, wheat bran leaching juice is added in fermentation medium, mevastatin is fermentation substrate, 146 159h are cultivated at 30 32 DEG C, incubation controls concentration of the mevastatin in zymotic fluid to obtain Pravastatin after fermented and cultured, Pravastatin content reaches more than 18g/L for 0.8~1.0g/L.The method of the present invention can significantly improve tolerance of the Actinomycesa lmadurae to mevastatin, concentration of the mevastatin in zymotic fluid is up to 0.8~1.0g/L, about 0.2g/L is improved than the prior art, improve conversion capability of the Actinomycesa lmadurae to mevastatin simultaneously, fermented and cultured terminates, and mevastatin conversion ratio reaches more than 74%.The method of the present invention is simple and practicable, at low cost, less energy consumption, and Pravastatin is mass produced available for industrialization.
Description
Technical field
The invention belongs to fermentation engineering fields, and in particular to a kind of method for improving Pravastatin fermentation yield.
Background technology
Pravastatin is 3- hydroxyl 3- methyl glutaryl coenzyme A reductase inhibitor, be used primarily for treatment hyperlipemia and
Familial high cholesterol, later indication constantly expand, and can slow down the development of atherosclerosis, and it is athero- to reduce coronary artery
Harden the generation of lesion and clinical cardiovascular events.Long-term use of Pravastatin, no matter whether patient with coronary heart disease, can subtract
The death rate caused by low a variety of causes, therefore, Pravastatin become only in current statins and can be used for cholesterol water
Flat higher or coronary heart disease patient carries out heart disease, the drug of apoplexy firsts and seconds defence.Also there is studies have shown that is general to cut down
Statin can also reduce diabetes and the incidence of Alzheimer disease；It can inhibit the multiplication of liver cancer cells；It can effectively treat routed
Ulcer colitis, few side effects, half a year recurrence rate are low；In terms of chronic heart failure, diastolic heart failure, it can improve
Heart function improves Ventricular Remodeling.
The production of Pravastatin is usually obtained by two-step fermentation process, although also have been reported that or patent (WO99/10499,
WO2007/147827, US 6,274,360 and EP 1,266,967) it describes that him can be cut down with the production acquisition of the method for one-step fermentation is general
Spit of fland, but due to technical sophistication and production efficiency etc., the industrialized production of Pravastatin is still based on two-step fermentation.It is general to cut down him
The two-step fermentation process in spit of fland is：First, produced and obtained by microbial fermentations such as Penicillium citrinums (Penicillium citrinum)
Its secondary metabolite mevastatin Mevastatin (also known as cameron Compactin) then, passes through the conversion of microbial enzyme
Effect, Pravastatin is converted by mevastatin.
Existing patent or documents and materials it is disclosed by mevastatin be converted into Pravastatin microorganism mainly include with
Under several classes：Filamentary mould (Mortierella maculata, WO00/46175), root mucor (Mucor Rhizopus,
US4448979), Nocard's bacillus (Norcardia, US5830695), Actinomycesa lmadurae (Actinomadura, WO96/
40863), streptomycete (Streptomyces Carbopilus EP215665), disleave streptomycete (Streptomyces
Exfoliates, WO98/45410) and whitewash Micropolyspora (Micropolysp ora roseoalba, CN03141475A)
Deng.
According to disclosed patent, above-mentioned mould, trichobacteria, actinomyces and streptomycete can convert mevastatin
Into Pravastatin.However, due to toxic action of the mevastatin to microorganism conversion bacterium so that microorganism is not resistant to be added to
The mevastatin of even low concentration in culture.Microorganism conversion bacterium is dense to the tolerance of substrate mevastatin under the prior art
It spends for 0.01-0.05%.
Although the disleave streptomycete YJ-118 that Li Zhouling etc. (WO98/45410) is obtained is demonstrated by higher (0.1-0.5%)
Substrate resistance, Metkinen (Metkinen News March 2000, Metkinen Oy, Finland；reviewed by
Manzoni and Rollini, 2002, Appl Microbiol Biotechnol 58：It 555-564) also obtains to 3g/L
The resistant Streptomyces mutant strains of mevastatin, but its Pravastatin yield is not high.
WO96/40863 discloses Actinomycesa lmadurae (Actinomadura) ATCC 55678 and converts mevastatin production
The method of Pravastatin, Chinese patent CN102757986B are disclosed using Actinomycesa lmadurae as transformed bacteria, during the fermentation
Using trace element solution to improve the method for Pravastatin yield, while it also studied fermented and cultured and control bacterium respectively in the process
Body Multiplying culture temperature and mevastatin conversion temperature are to the beneficial effect of Pravastatin output increased.But do not refer to bran both
The application of skin leaching juice wherein, does not refer to beneficial effect of the wheat bran leaching juice to Pravastatin output increased yet.
At present, Pravastatin fermenting and producing level is mostly in 15g/L or so, as the large-scale production of business application, so
Production level be still greatly improved space.
For two-step fermenting production Pravastatin, second step is Pravastatin by microorganism conversion mevastatin
It is the final steps for influencing Pravastatin yield, and in this step, how to improve microorganism and substrate mevastatin is turned
Change ability and Pravastatin fermentation level are to reduce Pravastatin production cost, increase Pravastatin yield to increase economic efficiency
Most effective approach.
The content of the invention
The object of the present invention is to provide a kind of wheat bran of addition in the fermentation medium leaching juice to improve Pravastatin yield
Method.Pravastatin yield is relatively low in existing process, and in order to overcome this defect, the present inventor is to the multinomial ginseng in entire technique
Number is studied, such as culture medium prescription and condition of culture in culture medium prescription in seed culture and condition of culture, fermented and cultured
Deng, finally found that, wheat bran leaching juice is added in into fermentation medium, can improve Actinomycesa lmadurae to the tolerance of mevastatin and
Conversion capability improves the fermentation level of Pravastatin, so as to improve the yield of Pravastatin.
It is provided by the invention it is a kind of improve Pravastatin fermentation yield method, be using mevastatin as fermentation substrate,
Wheat bran leaching juice is added in fermentation medium, passes through Actinomycesa lmadurae fermenting and producing Pravastatin.
In the inventive solutions, the wheat bran is the byproduct obtained after wheat processing flour.Past, wheat bran master
If as feed, economic value is not high.In fact, wheat bran contains nutritional ingredient, such as thiamines necessary to a large amount of microorganism growths
Auxin necessary to the growth of the microorganisms such as element, riboflavin, niacin, also containing a- amylase, beta amylase, oxidizing ferment, peroxide
Enzyme necessary to changing the growth of the microorganisms such as enzyme.And measured according to modern scientific research, p-aminobenzoic acid content is in plant in wheat bran
Highest, p-aminobenzoic acid is cell division necessary material.
The formula of fermentation medium of the present invention is：Glucose 56-58g/L, yeast extract 22-24g/L, soybean
Peptone 6-7g/L, K2HPO4·3H2O 1-2g/L、MgSO4·7H2O 0.5-1g/L、(NH4)2SO41-2g/L, wheat bran leaching juice
2.0-10.0ml/L and defomaing agent 0.5-1.0g/L, is prepared with water.
Preferably, in fermentation medium, wheat bran leaching juice 3-8ml/L.
Most preferably, in fermentation medium, wheat bran leaching juice 5.0ml/L.
Defomaing agent used in the present invention is known in the art common defomaing agent, the defomaing agent used in the embodiment of the present invention
For silicon ether defomaing agent.
The preparation method of wheat bran leaching juice is：Wheat bran is taken, adds in the water of 10~15 times of amounts of its weight, impregnates 2-8h, so
After heat, refluxing extraction 1h, filter liquor up to wheat bran soak juice.Filtering can be used but be not limited to multilayer filtered through gauze.
Further, in the method for raising Pravastatin fermentation yield of the invention, fermentation temperature is controlled always as 30-34
℃。
Preferably, fermentation temperature is 30-32 DEG C.
In the method for the raising Pravastatin fermentation yield of the present invention, Actinomycesa lmadurae has been inoculated with from mevastatin addition
Fermentation medium start to ferment, control concentration of the mevastatin in zymotic fluid as 0.6-1.0g/L, the duration is
Then 125-145h stops adding mevastatin, terminates fermentation after continuing fermentation 12-20h.
Preferably, since fermenting mevastatin addition has been inoculated with the fermentation medium of Actinomycesa lmadurae, control is beautiful
Concentration of the statin in zymotic fluid is cut down as 0.8-1.0g/L, duration 130-145h, then stops adding mevastatin, after
Terminate fermentation after supervention ferment 12-16h.
The present invention provides application of the wheat bran leaching juice in Pravastatin fermentation yield is improved.
The application is 2- with wheat bran leaching juice concentration in the fermentation medium of Actinomycesa lmadurae fermentation mevastatin
10g/L。
Specifically, the specific formula of the fermentation medium be glucose 56-58g/L, it is yeast extract 22-24g/L, big
Legumin peptone 6-7g/L, K2HPO4·3H2O 1-2g/L、MgSO4·7H2O 0.5-1g/L、(NH4)2SO41-2g/L, wheat bran leaching
Juice 2.0-10.0ml/L and defomaing agent 1.0g/L, is prepared with water.
In an embodiment of the present invention, shown in being as follows：
Step 1 seed culture：Seed culture medium is prepared first, in accordance with following formula：Glucose 28g/L, yeast extract
22g/L, soy peptone 7g/L, K2HPO4·3H2O 1g/L、MgSO4·7H2O 1g/L；It is inoculated with into above-mentioned seed culture medium
Actinomycesa lmadurae, when culture 60 is small at 32~34 DEG C after inoculation；
Step 2 fermented and cultured：Fermentation medium is prepared first, in accordance with following formula：56~58g/L of glucose, yeast extraction
22~24g/L of object, 6~7g/L of soy peptone, K2HPO4·3H21~2g/L of O, MgSO4·7H20.5~1g/L of O, (NH4)2SO41~2g/L, wheat bran leaching juice 5.0ml/L and defomaing agent 1.0g/L；Into fermentation medium, inoculation is after step 1 seed culture
Actinomycesa lmadurae, after inoculation first at 32~34 DEG C culture 30~40 it is small when, then adjust fermentation medium temperature be 30
Fill into mevastatin solution after~32 DEG C, when culture 146~159 is small at 30~32 DEG C, incubation control mevastatin is being sent out
Concentration in zymotic fluid is 0.8~1.0g/L.After fermented and cultured, the content of Pravastatin and mevastatin is detected, is as a result sent out
For the conversion ratio of existing mevastatin up to more than 74%, Pravastatin fermenting and producing is horizontal to reach more than 18g/L.Compared with prior art,
Up to more than 20%, conversion ratio is improved up to more than 10% production level increase rate, thus illustrates that the zymotechnique of the present invention can be big
Amplitude improves Pravastatin production efficiency and its yield.
In above-mentioned zymotechnique, used glucose, yeast extract, soybean in seed culture medium and fermentation medium
Common carbon source and nitrogen source ingredient, those skilled in the art exist when peptone carries out culture medium preparation for those skilled in the art
Common glucose, yeast extract and soy peptone when commercially available culture medium is prepared need to be only bought when realizing the present invention
Realize the present invention；The seed culture operation of the present invention and parameter use the prior art；The present invention fermented and cultured except
The wheat bran leaching juice added in culture medium, remaining operation and parameter use the prior art.
Compared with prior art, the present invention has the advantages that：
(1) inventor has found that wheat bran leaching juice has Actinomycesa lmadurae good growth promoting function, can improve Madura
(concentration of the mevastatin in zymotic fluid carries tolerance of the actinomyces to mevastatin up to 0.8~1.0g/L than the prior art
High about 0.2g/L), while improve Actinomycesa lmadurae (fermented and cultured terminates, and mevastatin turns to the conversion capability of mevastatin
Rate reaches more than 74%) and Pravastatin fermentation level (fermented and cultured terminates, and Pravastatin content reaches more than 18g/L),
So as to improve Pravastatin yield, production cost is reduced.
(2) zymotechnique of the invention is easy to operate, of low cost, is suitable for producing on a large scale.
Specific embodiment
The content that following embodiment further illustrates the present invention, but should not be construed as limiting the invention.Without departing substantially from
In the case of spirit and essence of the invention, to the modifications or substitutions that the method for the present invention, step or condition are made, the present invention is belonged to
Scope.
Unless otherwise specified, the conventional means that technological means used in embodiment is well known to those skilled in the art,
In embodiment, each raw material is added in unless otherwise indicated, be commercially available.
The Actinomycesa lmadurae (Actinomadura) of the present invention can cut down U.S.A using in any existing open source literature
Statin is converted into the strain of the actinomadura of Pravastatin, and the present invention can be achieved.
In following embodiments, Pravastatin and mevastatin content are according to such as Han Ming work《HPLC methods measure Pravastatin life
Produce the content of related component in sample》Pharmacy today .2010, the method for 20 (7) are detected.It is beautiful in the embodiment of the present invention
The conversion ratio of statin is cut down to be calculated with following formula：Conversion ratio=Pravastatin acquisition amount ÷ mevastatins usage amount ×
100%.
The fermentation process of the Actinomycesa lmadurae conversion mevastatin production Pravastatin of embodiment 1
What the wheat bran leaching juice of the present embodiment was prepared as follows：Wheat bran is taken, adds in the water of 15 times of amounts of its weight, is impregnated
Then 4h is heated, refluxing extraction 1h, using 6 layers of filtered through gauze, obtains wheat bran leaching juice.
1st, step 1 seed culture：
350mL seed culture mediums are prepared with 1L shaking flasks first, in accordance with following formula：Glucose 28g/L, yeast extract
22g/L, soy peptone 7g/L, K2HPO4·3H2O 1g/L、MgSO4·7H2O 1g/L and defomaing agent 1g/L.
Inclined-plane seed Actinomycesa lmadurae (Actinomadura) is accessed after seed culture medium sterilizing, is shaken at 32~34 DEG C
Bed culture 60h.
2nd, step 2 fermented and cultured
3L fermentation mediums are prepared with 5L automatic fermenters first, in accordance with following formula：Glucose 56g/L, yeast extraction
Object 22g/L, soy peptone 7g/L, K2HPO4·3H2O1g/L, MgSO4·7H2O 1g/L, (NH4)2SO41g/L, wheat bran leaching juice
5.0ml/L, defomaing agent 1g/L.
300mL seed liquors are accessed after fermentation medium sterilizing, when Multiplying culture 40 is small at 32~34 DEG C, adjust fermentation temperature
It spends for 30~32 DEG C and keeps this temperature in microorganism conversion mevastatin process, fill into mevastatin solution, examined with HPLC methods
Surveying mevastatin concentration makes it maintain 0.8~1.0g/L, stops adding mevastatin solution after cultivating to 170h, culture is extremely
Terminate fermentation after 186h, it is respectively 18116mg/L and 21mg/L to detect Pravastatin content and mevastatin content, is added in altogether beautiful
Cut down statin 73.5g, conversion ratio is up to 74%.When the Multiplying culture time in the present embodiment in fermentation medium is 40 small, Madura
Actinomyces conversion mevastatin is time of Pravastatin when being 146 small (when 186-40=146 is small).
The fermentation process of the Actinomycesa lmadurae conversion mevastatin production Pravastatin of embodiment 2
The present embodiment uses 50L automatic fermenters, with Actinomycesa lmadurae conversion mevastatin production Pravastatin, tool
Body step is as follows：What the wheat bran leaching juice of the present embodiment was prepared as follows：Wheat bran is taken, adds in 10 times of amounts of its weight
Water impregnates 4h, then heats, refluxing extraction 1h, using 6 layers of filtered through gauze, obtains wheat bran leaching juice.
Seed culture method is the same as embodiment 1.
Fermented and cultured operation is as follows：30L fermentation mediums are prepared first, in accordance with following formula：Glucose 58g/L, ferment
Female extract 24g/L, soy peptone 6g/L, K2HPO4·3H2O 2g/L, MgSO4·7H2O 0.5g/L, (NH4)2SO4 2g/
L, wheat bran leaching juice 5.0ml/L, defomaing agent 1g/L.
2.5L seed liquors are accessed after fermentation medium sterilizing, when culture 30 is small at 32~34 DEG C, adjusting fermentation temperature is
30~32 DEG C and this temperature is kept in microorganism conversion mevastatin process, fill into mevastatin solution, detected with HPLC methods beautiful
Cutting down statin concentration makes it maintain 0.8~1.0g/L, cultivate to 175 it is small when after stop add mevastatin solution, cultivate to 189
Terminate fermentation after hour, it is respectively 18433mg/L and 13mg/L to detect Pravastatin content and mevastatin content, is added in altogether beautiful
Cut down statin 797.1g, conversion ratio is up to 75%.
When the Multiplying culture time in the present embodiment in fermentation medium is 30 small, Actinomycesa lmadurae conversion mevastatin
When time for Pravastatin is 159 small.
3 reference examples of embodiment
The present embodiment uses 50L automatic fermenters, with Actinomycesa lmadurae conversion mevastatin production Pravastatin.This
Wheat bran leaching juice is not added in embodiment fermentation medium, remaining parameters is consistent with embodiment 2.Implementation steps are as follows：
Seed culture method is the same as embodiment 1.
Fermented and cultured operation is as follows：30L fermentation mediums are prepared first, in accordance with following formula：Glucose 58g/L, ferment
Female extract 24g/L, soy peptone 6g/L, K2HPO4·3H2O 2g/L, MgSO4·7H2O 0.5g/L, (NH4)2SO4 2g/
L, defomaing agent 1.0g/L.
2.5L seed liquors are accessed after fermentation medium sterilizing, control Multiplying culture temperature as 32~34 DEG C, when culture 30 is small,
It is 30~32 DEG C to convert cultivation temperature, fermented and cultured to 189 it is small when terminate, detect Pravastatin content and mevastatin content point
Not Wei 15016mg/L and 24mg/L, altogether add in mevastatin 762.5g, conversion ratio 64%.
In embodiment 3, fermentation medium does not add in wheat bran leaching juice, is the prior art.It is it turns out that (real with the prior art
Apply example 3) it compares, in the fermentation process of the embodiment of the present invention 2, due to adding wheat bran leaching juice in fermentation medium, fermentation is general to be cut down
Statin improves about 23% horizontally relative to embodiment 3, and mevastatin conversion ratio improves 11%.
Thus illustrate, addition wheat bran leaching juice can effectively improve Pravastatin fermentation level in fermentation medium and U.S.A cuts down him
The conversion ratio in spit of fland.
Although above the present invention is described in detail with a general description of the specific embodiments,
On the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Cause
This, these modifications or improvements, belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (10)
- A kind of 1. method for improving Pravastatin fermentation yield, which is characterized in that using mevastatin as fermentation substrate, trained in fermentation It supports and wheat bran leaching juice is added in base, pass through Actinomycesa lmadurae fermenting and producing Pravastatin.
- 2. the method as described in claim 1, which is characterized in that the formula of fermentation medium is：Glucose 56-58g/L, yeast Extract 22-24g/L, soy peptone 6-7g/L, K2HPO4·3H2O 1-2g/L、MgSO4·7H2O 0.5-1g/L、(NH4)2SO41-2g/L, wheat bran leaching juice 2.0-10.0ml/L and defomaing agent 0.5-1.0g/L, are prepared with water.
- 3. method as claimed in claim 2, which is characterized in that in fermentation medium, wheat bran leaching juice 3.0-8.0ml/L.
- 4. method as claimed in claim 2, which is characterized in that the preparation method of wheat bran leaching juice is：Wheat bran is taken, adds in it The water of 10~15 times of amounts of weight, impregnates 2-8h, then heats, refluxing extraction 1h, filters, and filtrate is taken to obtain wheat bran leaching juice.
- 5. the method as described in claim 1, which is characterized in that fermentation temperature is 30-34 DEG C.
- 6. method as claimed in claim 5, which is characterized in that fermentation temperature is 30-32 DEG C.
- 7. the method as described in claim 1-6 is any, which is characterized in that be inoculated with Actinomycesa lmadurae from mevastatin addition Fermentation medium start to ferment, control concentration of the mevastatin in zymotic fluid as 0.6-1.0g/L, the duration is Then 125-145h stops adding mevastatin, terminates fermentation after continuing fermentation 12-20h.
- 8. the method as described in claim 1-6 is any, which is characterized in that be inoculated with Actinomycesa lmadurae from mevastatin addition Fermentation medium start to ferment, control concentration of the mevastatin in zymotic fluid as 0.8-1.0g/L, the duration is Then 130-145h stops adding mevastatin, terminates fermentation after continuing fermentation 12-16h.
- 9. wheat bran soaks application of the juice in Pravastatin fermentation yield is improved.
- 10. application as claimed in claim 9, which is characterized in that with the fermented and cultured of Actinomycesa lmadurae fermentation mevastatin The formula of base is：Glucose 56-58g/L, yeast extract 22-24g/L, soy peptone 6-7g/L, K2HPO4·3H2O 1- 2g/L、MgSO4·7H2O 0.5-1g/L、(NH4)2SO41-2g/L, wheat bran leaching juice 2.0-10.0ml/L and defomaing agent 0.5- 1.0g/L is prepared with water.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115161355A (en) * | 2022-09-08 | 2022-10-11 | 上海现代制药股份有限公司 | Method for preparing high-stability pravastatin by using fermentation process |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102757986A (en) * | 2011-04-27 | 2012-10-31 | 广东蓝宝制药有限公司 | Fermentation process for producing pravastatin by transforming compactin by using actinomadura yumaense |
| CN105821086A (en) * | 2016-05-05 | 2016-08-03 | 广东蓝宝制药有限公司 | Process for producing pravastatin on large scale |
-
2016
- 2016-11-10 CN CN201610990905.7A patent/CN108070623A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102757986A (en) * | 2011-04-27 | 2012-10-31 | 广东蓝宝制药有限公司 | Fermentation process for producing pravastatin by transforming compactin by using actinomadura yumaense |
| CN105821086A (en) * | 2016-05-05 | 2016-08-03 | 广东蓝宝制药有限公司 | Process for producing pravastatin on large scale |
Non-Patent Citations (3)
| Title |
|---|
| Y PENG 等: ""A chemically-defined medium supporting growth and providing cells converting compactin to pravastatin"", 《JOURNAL OF INDUSTRIAL MICROBIOLOGY AND BIOTECHNOLOGY》 * |
| 宋波 等: ""一株能分解纤维素放线菌的固态发酵研究"", 《生物技术》 * |
| 郑邦山 等: "《农副产品储藏与加工》", 30 April 2003, 中原农民出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115161355A (en) * | 2022-09-08 | 2022-10-11 | 上海现代制药股份有限公司 | Method for preparing high-stability pravastatin by using fermentation process |
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