CN107723325A - Doractin fermentation method for producing based on pH controls - Google Patents
Doractin fermentation method for producing based on pH controls Download PDFInfo
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- C12P19/62—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin the hetero ring having eight or more ring members and only oxygen as ring hetero atoms, e.g. erythromycin, spiramycin, nystatin
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Abstract
The present invention relates to microbial medicine technical field, and in particular to the doractin fermentation method for producing based on pH controls.It the described method comprises the following steps：In the doractin producing strains primary metabolite stage, by basal medium mycelia fast-growth, pH is not controlled；PH is controlled in the range of 6.7 7.0 by adding physiological alkalinity salt, stream plus the first carbon source in the cometabolism stage.The method according to the invention can promote the quick increase that doractin synthesizes, and maintain prolonged Fast back-projection algorithm speed.This method is simple for process, easily operated, is especially suitable for commercially producing.
Description
Technical field
The present invention relates to microbial medicine technical field, and in particular to the doractin fermenting and producing side based on pH controls
Method.
Background technology
Doractin (doramectin) is macrolides antiparasitic agent of new generation, is the hexamethylene of AVERMECTIN B1
Carboxylic acid (cyclohexanecarboxylicacid, CHC) precursor isomeric compound (i.e. 25- cyclohexyls AVERMECTIN B1), pass through Ah
It is that precursor can biology to tie up and cyclohexane-carboxylic acid is added in streptomycete (Streptomyces avermitilis) mutant strain fermentation process
Synthesize doractin.Because doractin has anti parasitic is in extensive range (it is quick to its to share the mesh 73 of 3 guiding principle 12 category parasite in clinical
Sense), significant effect, method of administration is easy to grasp, the advantage such as bioavilability is high, medicine longevity of residure length, should in veterinary clinic
For mammals such as ox, horse, sheep, goat, pig, camel, dogs.The structural formula of doractin is as follows：
The fermentation process of microorganism is generally divided into two stages of primary metabolite and cometabolism.In the primary metabolite stage, master
Meet mycelial growth, it is desirable to provide base stock such as glucose and phosphate needed for fast-growth, also include certainly
It is easy to the nitrogen source utilized.Doramectin preparing bacterium strain Avid kyowamycin can be with fast-growth near pH7.0.As thalline is quick
Growth, a large amount of organic acids caused by primary metabolite are gradually reduced zymotic fluid pH, and fermentation process enters the cometabolism stage.Duola
The biosynthesis of rhzomorph needs suitable pH scopes, and too high or too low pH value is unfavorable for the synthesis of target product.
The content of the invention
In view of the shortcomings of the prior art, the invention provides it is a kind of based on pH control doractin fermentation method for producing,
Different pH scopes are controlled by the different phase in doractin producing strains fermentation process, obtain that synthesis rate is fast, fermentation
The high doractin zymotechnique of yield.
The concrete technical scheme of the present invention is as follows：
The invention provides a kind of doractin fermentation method for producing based on pH controls, comprise the following steps：
In the doractin producing strains primary metabolite stage, by basal medium mycelia fast-growth, pH is not controlled
System；PH is controlled in the range of 6.7-7.0 by adding physiological alkalinity salt, stream plus the first carbon source in the cometabolism stage.
According to an embodiment of the invention, the basal medium contains phosphate and second carbon source.
According to an embodiment of the invention, the physiological alkalinity salt is selected from tricresyl phosphate magnesium, tricresyl phosphate magnesium hydrate (example
Such as four water tricresyl phosphate magnesium, five water tricresyl phosphate magnesium), potassium acetate and sodium acetate etc. more than one.
According to an embodiment of the invention, first carbon source is selected from starch, glucose, dextrin, maltose and wheat
One or more of bud dextrin.
According to an embodiment of the invention, in the cometabolism stage, every liter of zymotic fluid relatively, the physiological alkalinity salt
Addition be no more than 3 grams/L, the addition of first carbon source is 30-60 grams/L.
According to an embodiment of the invention, the phosphate is selected from dipotassium hydrogen phosphate, potassium dihydrogen phosphate, tricresyl phosphate
One or more of magnesium, tricresyl phosphate magnesium hydrate.
According to an embodiment of the invention, the second carbon source is selected from starch, glucose, maltose, dextrin, malt
One or more of dextrin.
According to an embodiment of the invention, in every liter of basal medium, the phosphatic addition is 2-9
Gram/L, the addition of the second carbon source is 90-110 grams.
According to an embodiment of the invention, also comprising 5-20 grams of soybean cake powder, cotton in every liter of basal medium
5-20 grams of seed cake powder, 1-5 grams of calcium carbonate, 0.5-1.5 grams of sodium chloride, 0.6-1.0 grams of defoamer, surplus are water.
According to an embodiment of the invention, it is in the condition of culture in primary metabolite stage and cometabolism stage：
27.5-29.5 DEG C of cultivation temperature, speed of agitator 80-220rpm, air mass flow 1:0.5-0.8vvm.
Present invention employs two sections of pH control strategies, doractin bacterium primary metabolite stage, by basal medium
Addition glucose and phosphate cause mycelia fast-growth, and pH is not controlled；PH shows as 0-90 hours from low to high, and highest is not
More than 7.2,6.3-6.5 was gradually decreased to by 120 hours or so afterwards.Afterwards in the cometabolism stage by adding physiological alkalinity
Salt, pH is controlled to meet the optimum pH required for doractin biosynthesis most preferably in 6.7-7.0 scopes with interflow plus carbon source,
Promote the quick increase of doractin synthesis, and maintain prolonged Fast back-projection algorithm speed, the doractin hair of 250-300 hours
Ferment yield is up to 2100-2300ug/ml.This method is simple for process, easily operated, is especially suitable for commercially producing.
Embodiment
With reference to embodiment, the embodiment of the present invention is described in further detail.Following examples are used for
Illustrate the present invention, but be not limited to the scope of the present invention.Present invention encompasses all possible in Claims scope
Alternative, improvement project and equivalents.Unreceipted particular technique or condition in following embodiments, be routine techniques or
Condition, or carried out according to the technology or condition described by document in the art, or according to product description.
In the present invention, the content of doractin is measured by HPLC efficient liquid phase detection methods, specific as follows.
Measuring column：C18 posts, 4.6mm × 250mm × 5um, column temperature：30℃；Using isocratic elution, mobile phase is methanol:
Water:Acetonitrile (8:1:1)；Flow velocity is 1.0mL/min；Detection wavelength：245nm；Sample size：10μL.According to area normalization method meter
Calculate the content of doractin.
Embodiment 1
Strain：Avid kyowamycin Streptomyces avermitilis ATCC 53568
Fermentation medium matches：
Accurate weigh up in starch input fermentation batches tank of proportioning (is previously added suitable quantity of water) according to the rules, starts stirring, adds
Enter the heating of amylase (the 0.5% of starch weight) steam, be gradually warming up to 85 DEG C, insulated and stirred 60 minutes, make the abundant liquid of starch
Change.Put into again by above-mentioned dispensing in material-compound tank and add water to constant volume, pH is surveyed in stirring after 15 minutes, pH requirements 6.9, risen
Temperature, when temperature reaches 121 DEG C, start sterilizing 30 minutes.
Fermentation volume：600L
Inoculum concentration：10%
Cultivation temperature：27.5-29.5℃
Speed of agitator：80-220rpm
Air mass flow：1:0.5-0.8vvm
Cultivation cycle：270-300 hours
In doractin producing strains earlier fermentation, by basal medium mycelia fast-growth, pH is not controlled.
Precursor is mended in fermentation：Cyclohexanecarboxylic acid is configured to sodium salt, fills into 0.18wt% cyclohexanecarboxylic acid sodium salt altogether.Fermentation tank
When cultivating 40hr, 0.08wt% cyclohexanecarboxylic acid is added；During fermentation tank culture 110-130hr, 0.05wt% hexamethylenes are added
Formic acid；0.05wt% cyclohexanecarboxylic acid is added during fermentation tank culture 210hrs-220hrs.
Sugar is mended in fermentation：During the cometabolism stage (fermentation 130-280 hours), maltodextrin solution (malt is filled into
In dextrin solution, the concentration of maltodextrin is 300 grams/L) and tricresyl phosphate magnesium suspension (in tricresyl phosphate magnesium suspension, tricresyl phosphate magnesium it is dense
Spend for 30.0 grams/L), total sugar content control controls the scope in 6.7-6.9 in 2.0-4.0% or so, pH.Repeatedly fill into respectively,
Add total amount：Every liter of zymotic fluid relatively, maltodextrin are 30.0 grams, and tricresyl phosphate magnesium is 1.5 grams.During fermentation, pH value control exists
6.7-6.9, the pH value of fermentation the 288th hour is 7.0.
2 milliliters of zymotic fluid is taken, 10 milliliters of ethanol is added, shakes 15 minutes, high speed centrifugation obtains supernatant, HPLC analysis Duola
The content of rhzomorph, the potency of the doractin of fermentation the 288th hour is 2.11 grams/L.
Embodiment 2
Strain：Avid kyowamycin Streptomyces avermitilis ATCC 53568
Fermentation medium matches：
Accurate weigh up in starch input fermentation batches tank of proportioning (is previously added suitable quantity of water) according to the rules, starts stirring, adds
Enter the heating of amylase (the 0.5% of starch weight) steam, be gradually warming up to 85 DEG C, insulated and stirred 60 minutes, make the abundant liquid of starch
Change.Put into again by above-mentioned dispensing in material-compound tank and add water to constant volume, pH is surveyed in stirring after 15 minutes, pH requirements 6.9, risen
Temperature, when temperature reaches 121 DEG C, start sterilizing 30 minutes.
Fermentation volume：600L
Inoculum concentration：10%
Cultivation temperature：27.5-29.5℃
Speed of agitator：80-220rpm
Air mass flow：1:0.5-0.8vvm
Cultivation cycle:270-300 hours
In doractin producing strains earlier fermentation, by basal medium mycelia fast-growth, pH is not controlled.
Precursor is mended in fermentation：Cyclohexanecarboxylic acid is configured to sodium salt, fills into 0.18wt% cyclohexanecarboxylic acid sodium salt altogether.Fermentation tank
When cultivating 40hr, 0.08wt% cyclohexanecarboxylic acid is added；During fermentation tank culture 110-130hr, 0.05wt% hexamethylenes are added
Formic acid；0.05wt% cyclohexanecarboxylic acid is added during fermentation tank culture 210hrs-220hrs.
Sugar is mended in fermentation：During the cometabolism stage (fermentation 130-280 hours), dextrin solution (dextrin solution is filled into
In, the concentration of dextrin is 300 grams/L), (in five water tricresyl phosphate magnesium suspensions, the concentration of tricresyl phosphate magnesium is 30.0 to tricresyl phosphate magnesium suspension
Gram/L) and liquor kalii acetici (in liquor kalii acetici, the concentration of potassium acetate is 10 grams/L), total sugar content control is in 2.0-5.0%
Left and right, pH control the scope in 6.7-6.9.Repeatedly fill into respectively, add total amount：Every liter of zymotic fluid relatively, dextrin are 40.0 grams,
Five water tricresyl phosphate magnesium are 1.6 grams, and potassium acetate is 0.6 gram.During fermentation, pH value is controlled in 6.7-7.0, is fermented the 300th hour
PH value is 7.1.
2 milliliters of zymotic fluid is taken, 10 milliliters of ethanol is added, shakes 15 minutes, high speed centrifugation obtains supernatant, HPLC analysis Duola
The content of rhzomorph, the potency of the doractin of fermentation the 300th hour is 2.18 grams/L.
Embodiment 3
Strain：Avid kyowamycin Streptomyces avermitilis ATCC 53568
Fermentation medium matches：
Accurate weigh up in starch input fermentation batches tank of proportioning (is previously added suitable quantity of water) according to the rules, starts stirring, adds
Enter the heating of amylase (the 0.5% of starch weight) steam, be gradually warming up to 85 DEG C, insulated and stirred 60 minutes, make the abundant liquid of starch
Change.Put into again by above-mentioned dispensing in material-compound tank and add water to constant volume, pH is surveyed in stirring after 15 minutes, pH requirements 6.9, risen
Temperature, when temperature reaches 121 DEG C, start sterilizing 30 minutes.
Fermentation volume：6000L
Inoculum concentration：10%
Cultivation temperature：27.5-29.5℃
Speed of agitator：80-220rpm
Air mass flow：1:0.5-0.8vvm
Cultivation cycle：270-300 hours
In doractin producing strains earlier fermentation, by basal medium mycelia fast-growth, pH is not controlled.
Precursor is mended in fermentation：Cyclohexanecarboxylic acid is configured to sodium salt, fills into 0.18wt% cyclohexanecarboxylic acid sodium salt altogether.Fermentation tank
When cultivating 40hr, 0.08wt% cyclohexanecarboxylic acid is added；During fermentation tank culture 110-130hr, 0.05wt% hexamethylenes are added
Formic acid；0.05wt% cyclohexanecarboxylic acid is added during fermentation tank culture 210hrs-220hrs.
Sugar is mended in fermentation：During the cometabolism stage (fermentation 130-280 hours), maltodextrin solution (malt is filled into
In dextrin solution, the concentration of maltodextrin is 300 grams/L), tricresyl phosphate magnesium suspension (in tricresyl phosphate magnesium suspension, tricresyl phosphate magnesium it is dense
Spend for 30.0 grams/L) and sodium acetate solution (in sodium acetate solution, the concentration of sodium acetate is 10 grams/L), total sugar content, which controls, to exist
2.0-4.0% or so, pH control the scope in 6.7-6.9.Repeatedly fill into respectively, add total amount：Every liter of zymotic fluid relatively, malt
Dextrin is 60.0 grams, and tricresyl phosphate magnesium is 2.3 grams, and sodium acetate is 0.5 gram.During fermentation, pH value control is in 6.7-7.0, fermentation the
The pH value of 288 hours is 7.0.
2 milliliters of zymotic fluid is taken, 10 milliliters of ethanol is added, shakes 15 minutes, high speed centrifugation obtains supernatant, HPLC analysis Duola
The content of rhzomorph, the potency of the doractin of fermentation the 298th hour is 2.25 grams/L.
Embodiment 4
Strain：Avid kyowamycin Streptomyces avermitilis ATCC 53568
Fermentation medium matches：
Accurate weigh up in starch input fermentation batches tank of proportioning (is previously added suitable quantity of water) according to the rules, starts stirring, adds
Enter the heating of amylase (the 0.5% of starch weight) steam, be gradually warming up to 85 DEG C, insulated and stirred 60 minutes, make the abundant liquid of starch
Change.Put into again by above-mentioned dispensing in material-compound tank and add water to constant volume, pH is surveyed in stirring after 15 minutes, pH requirements 6.9, risen
Temperature, when temperature reaches 121 DEG C, start sterilizing 30 minutes.
Fermentation volume：600L
Inoculum concentration：10%
Cultivation temperature：27.5-29.5℃
Speed of agitator：80-220rpm
Air mass flow：1:0.5-0.8vvm
Cultivation cycle：270-300 hours
In doractin producing strains earlier fermentation, by basal medium mycelia fast-growth, pH is not controlled.
Precursor is mended in fermentation：Cyclohexanecarboxylic acid is configured to sodium salt, fills into 0.18wt% cyclohexanecarboxylic acid sodium salt altogether.Fermentation tank
When cultivating 40hr, 0.08wt% cyclohexanecarboxylic acid is added；During fermentation tank culture 110-130hr, 0.05wt% hexamethylenes are added
Formic acid；0.05wt% cyclohexanecarboxylic acid is added during fermentation tank culture 210hrs-220hrs.
Sugar is mended in fermentation：During the cometabolism stage (fermentation 130-280 hours), maltodextrin solution (malt is filled into
In dextrin solution, the concentration of maltodextrin is 300 grams/L) and tricresyl phosphate magnesium suspension (in tricresyl phosphate magnesium suspension, tricresyl phosphate magnesium it is dense
Spend for 30.0 grams/L), total sugar content is controlled in 2.0-4.0% or so, adds total amount：Every liter of zymotic fluid, maltodextrin are relatively
45.0 grams, tricresyl phosphate magnesium is 2.5 grams.During fermentation, in 6.7-6.9, the pH value fermented the 288th hour is 7.0 for pH value control.
2 milliliters of zymotic fluid is taken, 10 milliliters of ethanol is added, shakes 15 minutes, high speed centrifugation obtains supernatant, HPLC analysis Duola
The content of rhzomorph, the potency of the doractin of fermentation the 288th hour is 2.13 grams/L.
Comparing embodiment 1
Carbon source maltodextrin has only been added with differing only in when fermentation mends sugared for embodiment 4, has not added physiological alkalinity salt
Tricresyl phosphate magnesium.During fermentation, pH value is minimum to reach 6.2, gradually gos up to 6.7 within the 280th hour in fermentation, ferments the 300th hour
PH value be 7.2.
2 milliliters of zymotic fluid is taken, 10 milliliters of ethanol is added, shakes 15 minutes, high speed centrifugation obtains supernatant, HPLC analysis Duola
The content of rhzomorph, the potency of the doractin of fermentation the 300th hour is 1.45 grams/L.
According to an embodiment of the invention in 1-4, fermentation stage by adding the physiological alkalinity salt such as tricresyl phosphate magnesium, potassium acetate,
With the carbon source such as interflow plus maltodextrin, dextrin, control pH most preferably in 6.7-7.0 scopes, promotes the quick increasing of doractin synthesis
Add, and maintain prolonged Fast back-projection algorithm speed, doractin potency can reach 2.2 grams/L.In comparing embodiment 1, fermentation
Stage has only added carbon source, does not add physiological alkalinity salt, ferments the middle and later periods, and pH value is unstable, and it is relatively low to show as mid-term pH value, effect
Valency is increasesd slowly, later stage pH value rapid increase, and potency, which increases, to be stagnated, the fermentation unit of three embodiments than carrying out pH value control
Relatively low more than 30%.
As can be seen here, the method according to the invention can make the pH of doractin Fermentation Engineering control the model in 6.7-7.0
Enclose, meet the optimum pH required for doractin biosynthesis, promote doractin synthesis, and remain prolonged and quickly close
Into speed.
Obviously, those skilled in the art can carry out the essence of various changes and modification without departing from the present invention to the present invention
God and scope.So, if these modifications and variations of the present invention belong to the scope of the claims in the present invention and its equivalent technologies
Within, then the present invention is also intended to comprising including these changes and modification.
Claims (10)
1. a kind of doractin fermentation method for producing based on pH controls, it is characterised in that comprise the following steps：
In the doractin producing strains primary metabolite stage, by basal medium mycelia fast-growth, pH is not controlled；
The cometabolism stage controls pH in the range of 6.7-7.0 by adding physiological alkalinity salt, stream plus the first carbon source.
2. doractin fermentation method for producing according to claim 1, it is characterised in that the basal medium contains phosphorus
Hydrochlorate and second carbon source.
3. doractin fermentation method for producing according to claim 1, it is characterised in that the physiological alkalinity salt is selected from phosphorus
One or more of sour three magnesium, tricresyl phosphate magnesium hydrate, potassium acetate and sodium acetate.
4. doractin fermentation method for producing according to claim 1, it is characterised in that first carbon source, which is selected from, forms sediment
One or more of powder, glucose, dextrin, maltose and maltodextrin.
5. doractin fermentation method for producing according to claim 1, it is characterised in that in the cometabolism stage, relatively
Every liter of zymotic fluid, the addition of the physiological alkalinity salt be no more than 3 grams/L, the addition of first carbon source for 30-60 grams/
L。
6. doractin fermentation method for producing according to claim 2, it is characterised in that the phosphate is selected from phosphoric acid hydrogen
One or more of dipotassium, potassium dihydrogen phosphate, tricresyl phosphate magnesium, tricresyl phosphate magnesium hydrate.
7. doractin fermentation method for producing according to claim 2, it is characterised in that the second carbon source, which is selected from, to form sediment
One or more of powder, glucose, maltose, dextrin, maltodextrin.
8. doractin fermentation method for producing according to claim 2, it is characterised in that every liter of basal medium
In, the phosphatic content is 2-9 grams, and the content of the second carbon source is 90-110 grams.
9. doractin fermentation method for producing according to claim 1, it is characterised in that in every liter of basal medium
Also comprising 5-20 grams of soybean cake powder, 5-20 grams of cottonseed meal, 1-5 grams of calcium carbonate, 0.5-1.5 grams of sodium chloride, defoamer 0.6-1.0
Gram, surplus is water.
10. doractin fermentation method for producing according to claim 1, it is characterised in that the primary metabolite stage and time
Level metabolic stage condition of culture be：27.5-29.5 DEG C of cultivation temperature, speed of agitator 80-220rpm, air mass flow 1:0.5-
0.8vvm。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110846371A (en) * | 2019-11-27 | 2020-02-28 | 湖北共同生物科技有限公司 | Steroid precursor fermentation production method for improving activity of steroid production strain |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1202493A (en) * | 1993-10-05 | 1998-12-23 | 美国辉瑞有限公司 | Intermediate of doramectin for antiparastic chemical and its preparing method |
| CN1265113A (en) * | 1997-07-23 | 2000-08-30 | 美国辉瑞有限公司 | Prodn. method of avermectin compounds |
| CN104561180A (en) * | 2014-12-26 | 2015-04-29 | 宁夏泰瑞制药股份有限公司 | Culture mediums for producing doramectin through fermentation of mutant streptomyces avermitilis and material supplement method |
| CN104651427A (en) * | 2015-01-21 | 2015-05-27 | 丽珠集团新北江制药股份有限公司 | Method for preparing doramectin |
| CN105586374A (en) * | 2014-10-22 | 2016-05-18 | 重庆乾泰生物医药有限公司 | Process for producing doramectin with carbohydrate supplementation based on metabolic parameter reducing sugar |
-
2017
- 2017-11-28 CN CN201711215737.5A patent/CN107723325B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1202493A (en) * | 1993-10-05 | 1998-12-23 | 美国辉瑞有限公司 | Intermediate of doramectin for antiparastic chemical and its preparing method |
| CN1265113A (en) * | 1997-07-23 | 2000-08-30 | 美国辉瑞有限公司 | Prodn. method of avermectin compounds |
| CN105586374A (en) * | 2014-10-22 | 2016-05-18 | 重庆乾泰生物医药有限公司 | Process for producing doramectin with carbohydrate supplementation based on metabolic parameter reducing sugar |
| CN104561180A (en) * | 2014-12-26 | 2015-04-29 | 宁夏泰瑞制药股份有限公司 | Culture mediums for producing doramectin through fermentation of mutant streptomyces avermitilis and material supplement method |
| CN104651427A (en) * | 2015-01-21 | 2015-05-27 | 丽珠集团新北江制药股份有限公司 | Method for preparing doramectin |
Non-Patent Citations (2)
| Title |
|---|
| CHRISTOPHER J. DUTTON: "NOVEL AVERMECTINS PRODUCED BY MUTATIONAL BIOSYNTHESIS", 《THE JOURNAL OF ANTIBIOTICS》 * |
| 白宝星: "突变生物合成在微生物药物领域的研究进展", 《中国抗生素杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110846371A (en) * | 2019-11-27 | 2020-02-28 | 湖北共同生物科技有限公司 | Steroid precursor fermentation production method for improving activity of steroid production strain |
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