CN1075167A - The manufacture method of mydecamycin - Google Patents
The manufacture method of mydecamycin Download PDFInfo
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- CN1075167A CN1075167A CN 93110080 CN93110080A CN1075167A CN 1075167 A CN1075167 A CN 1075167A CN 93110080 CN93110080 CN 93110080 CN 93110080 A CN93110080 A CN 93110080A CN 1075167 A CN1075167 A CN 1075167A
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- China
- Prior art keywords
- mydecamycin
- hours
- propionic acid
- acid amide
- fermented liquid
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention provides a kind of method of manufacture order component mydecamycin.In the fermention medium that produces bacterium change strain, add propionic acid amide, just can make the mydecamycin A in the product
1Content is improved significantly.The characteristics of this method are that technology is simple, and are reliable for effect.
Description
The present invention relates to a kind of fermentation process that propionic acid amide is produced mydecamycin that in fermention medium, adds.
Mydecamycin belongs to Macrolide polycomponent microbiotic, in respect of A
1, A
2, A
3, A
4Four components, as medicinal mainly be wherein A
1Component.China Ministry of Health regulation, the antibiotic major constituent content of the full biosynthesizing of single component should be not less than 80%.External mydecamycin is with the A in the kind
1The content majority is all more than 80%." mydecamycin " that China's bacterial strain is produced all is the polycomponent product for a long time, removes to contain a certain amount of A
1The leucomycin A that also has a great deal of outward,
6Etc. component.Unresolved for many years this problem causes China can only produce the polycomponent product, and this product is renamed as " Meleumycinum " (meleumycin), stipulates wherein A
1Content (external standard method) 35%, tire more than 850 μ g/mg.Leucomycin A
6To the antibiotic vigor of pathogenic bacterias such as golden Portugal bacterium 15, pneumococcus 31103 than mydecamycin A
1Little 2-4 doubly.Thereby the curative effect of Meleumycinum is affected.
Mydecamycin is the sixteen-ring macrolide antibiotic, contains aglycon, the mould aminosugar of carbon, three parts of mycaminose in its molecular structure.Because aglycon C
3-OH and mycaminose C
4 "The last acyl substituent difference of-OH can form different components.Mydecamycin A
1With leucomycin A
6Chemical structural formula be:
Mydecamycin A
1Component R=COCH
2CH
3
Leucomycin A
6Component R=COCH
3
Mydecamycin A
1C
3Substituting group on the-OH is a propionyl, and leucomycin A
6It is ethanoyl.
Obtain the full biosynthesizing microbiotic of single component, can adopt the gene that change antibiotics generated bacterium, improve the method for precursor output; Also can adopt the method that in fermention medium, directly adds precursor substance.Do not see the biology of manufacture order component mydecamycin or the report of producing and manufacturing technique so far as yet.
The object of the present invention is to provide a kind of method of producing mydecamycin, synthesize mydecamycin A as precursor substance with propionic acid amide
1Novel process.
The present invention is according to the biosynthesizing principle of wheat enlightening (in vain) mycin, the raising mydecamycin A that designs
1This method of output.In the fermention medium that produces bacterium change strain, add propionic acid amide, the mydecamycin A in the fermented liquid
1Content just improves the 10-40%(area normalization method than the reference substance that does not add propionic acid amide), A
1Increasing amount relevant with the add-on and the joining day of propionic acid amide.
As shown in table 1, Streptomyces Macrofaciens 1748 becomes strains in shaking bottle shaking culture, at different fermentation times, the aseptic propionamide solution that adds 100-300mg% in fermention medium, the mydecamycin A in the fermented liquid
1All increases of showed different of content, added at 12 hours especially, increase the most obvious.
Annotate: testing used fermention medium is starch 1.0%, sucrose 4.0%, analysis for soybean powder 3.0%, fish meal 0.2%, yeast powder 0.2%, potassium primary phosphate 0.1%, sal epsom 0.1%, lime carbonate 0.15%.The 250ml triangular flask, loading amount 20ml, the seed of access Streptomyces Macrofaciens, in 28 ℃, shaking culture 2 days adds the different propionic acid amide sterilized solutions of measuring at different incubation times.After the cultivation, through centrifugation, supernatant liquor send the high pressure liquid phase analysis component.
The object of the present invention is achieved like this: Streptomyces Macrofaciens 1748 is become strain (Streptomyces mycarofaciens var.1748) earlier in sterilization, cooled seed culture medium (consisting of glucose, starch, analysis for soybean powder, ammonium sulfate, potassium primary phosphate, lime carbonate), cultivated 48 hours, and promptly got the seed liquor that produces bacterium for 28 ℃;
Seed liquor with gained, change in sterilization, the cooled fermention medium (consisting of glucose, starch, analysis for soybean powder, yeast powder, sal epsom, potassium primary phosphate, lime carbonate) by 15% inoculum size, 28 ℃ of aeration-agitations are cultivated, in fermentation 24 hours, gradation adds the aseptic propionamide solution that its total amount is 0.1-0.8%, cultivated 48 hours, and promptly got fermented liquid.
The gained fermented liquid is handled routinely, and filtration, extraction, crystallization, drying promptly get the mydecamycin finished product.
Advantage of the present invention is: utilizing the component of the mydecamycin product of described method production, almost mainly is mydecamycin A
1, content reaches the 80%(external standard method) more than, and do not add the A of the experimental control product of propionic acid amide
1Content only is about 50%.This is very favorable from the industrial production angle.The characteristics of this method are that technology is simple, reliable for effect.
Embodiment 1:
Streptomyces Macrofaciens 1748 becomes strain, in the aseptic seed substratum of seeding tank, cultivates 48 hours for 28 ℃ earlier.Seed culture medium consist of glucose 3.0%, starch 1.0%, analysis for soybean powder 2.0%, ammonium sulfate 0.5%, potassium primary phosphate 0.05%, lime carbonate 0.3%.The gained seed culture fluid changes the 300l that is contained in the 500l fermentor tank over to by 15% inoculum size not to be had in the bacteria fermentation culture medium.Fermention medium consist of glucose 1.0%, starch 3.0%, analysis for soybean powder 3.0%, yeast powder 0.2%, sal epsom 0.1%, potassium primary phosphate 0.1%, lime carbonate 0.1%.Carry out aeration-agitation at 28 ℃ and cultivate, air flow is 1vvm, and mixing speed is 250r.p.m, cultivates 48 hours, just makes the mydecamycin fermented liquid.
In culturing process,, add 0.1%, 0.2% the propionic acid amide solution that bacterium is crossed in death of monks or nuns respectively in fermentation initial sum in the time of 12 hours.The fermentation unit of fermentation termination for do not add propionic acid amide control fermentation liquid fermentation unit 90%.
The fermented liquid of gained is handled through routine, and filtration, extraction, crystallization, drying promptly get the mydecamycin product.Mydecamycin A in the product
1Content reaches the 84%(external standard method), tiring, to reach 980 μ g/mg(be test organisms with the Bacillus subtilus), and do not add the A of the experimental control product of propionic acid amide
1Content is 53.8% only, and tiring is 910 μ g/mg.
Embodiment 2:
The composition of seed culture medium and fermention medium is with embodiment 1.In the 500l fermentor tank, the 300l fermention medium of packing into after the sterilization cooling, inserts the seed culture fluid that Streptomyces Macrofaciens 1748 becomes strain, and mixing speed is 250r.p.m., and air flow is 1vvm, cultivates 48 hours in 28 ℃ of aeration-agitations, promptly gets the mydecamycin fermented liquid.
In culturing process,, add 0.05%, 0.1% the propionic acid amide solution that bacterium is crossed in death of monks or nuns respectively in fermentation initial sum in the time of 12 hours.Consequently, fermentation unit for do not add propionic acid amide contrast 95%, the mydecamycin A in the product
1Content reaches 81%, tires to reach 950 μ g/mg, and does not add the A of the experimental control product of propionic acid amide
1Content is 51.9%, and tiring is 905 μ g/mg.
Embodiment 3:
Seed culture medium and the composition of sending out substratum pure are with embodiment 1.In the 500l fermentor tank, the 300l fermention medium of packing into after the sterilization cooling, inserts the seed culture fluid that Streptomyces Macrofaciens 1748 becomes strain, and mixing speed is 250r.p.m., and air flow is 1vvm, cultivates 48 hours in 28 ℃ of aeration-agitations, promptly gets the mydecamycin fermented liquid.
In culturing process,, add 0.1%, 0.3% the propionic acid amide solution that bacterium is crossed in death of monks or nuns respectively in fermentation initial sum in the time of 20 hours.Consequently, fermentation unit for do not add propionic acid amide contrast 96%, the mydecamycin A in the product
1Content reaches 82%, tires to reach 955 μ g/mg, and does not add the A of the experimental control product of propionic acid amide
1Content is 52.4%, and tiring is 910 μ g/mg.
Claims (1)
1, a kind of production chemical structural formula is
The method of mydecamycin is characterized in that:
A. Streptomyces Macrofaciens 1748 is become strain (Streptomycesmycarofaciensvar.1748) in seed culture medium, cultivated 48 hours, and promptly got the seed liquor that produces bacterium for 28 ℃;
B. with the seed liquor of gained, change in the fermention medium by 15% inoculum size, 28 ℃ of aeration-agitations are cultivated, and in fermentation 24 hours, gradation adds the aseptic propionamide solution that its total amount is 0.1-0.8%, cultivates 48 hours, promptly gets fermented liquid;
C. the gained fermented liquid is handled routinely, filtration, extraction, crystallization, drying are finished product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 93110080 CN1075167A (en) | 1993-02-12 | 1993-02-12 | The manufacture method of mydecamycin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 93110080 CN1075167A (en) | 1993-02-12 | 1993-02-12 | The manufacture method of mydecamycin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1075167A true CN1075167A (en) | 1993-08-11 |
Family
ID=4987988
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 93110080 Pending CN1075167A (en) | 1993-02-12 | 1993-02-12 | The manufacture method of mydecamycin |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1094979C (en) * | 1996-02-09 | 2002-11-27 | 吉斯特·布罗卡迪斯股份有限公司 | Natamycin recovery |
| CN102532222A (en) * | 2010-12-21 | 2012-07-04 | 北大方正集团有限公司 | Catalyzing method of medecamycin |
| CN102676617A (en) * | 2011-03-17 | 2012-09-19 | 河南天方药业股份有限公司 | Preparation method for meleumycin |
| CN108977481A (en) * | 2017-11-08 | 2018-12-11 | 北大方正集团有限公司 | A kind of method of fermenting and producing meleumycin |
-
1993
- 1993-02-12 CN CN 93110080 patent/CN1075167A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1094979C (en) * | 1996-02-09 | 2002-11-27 | 吉斯特·布罗卡迪斯股份有限公司 | Natamycin recovery |
| CN102532222A (en) * | 2010-12-21 | 2012-07-04 | 北大方正集团有限公司 | Catalyzing method of medecamycin |
| CN102532222B (en) * | 2010-12-21 | 2015-06-17 | 北大方正集团有限公司 | Catalyzing method of medecamycin |
| CN102676617A (en) * | 2011-03-17 | 2012-09-19 | 河南天方药业股份有限公司 | Preparation method for meleumycin |
| CN108977481A (en) * | 2017-11-08 | 2018-12-11 | 北大方正集团有限公司 | A kind of method of fermenting and producing meleumycin |
| CN108977481B (en) * | 2017-11-08 | 2021-08-27 | 北大方正集团有限公司 | Method for producing meleumycin by fermentation |
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