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Method for fermentation production of clavulanic acid

A technology of clavulanic acid and fermentation culture, which is applied in the field of biomedicine, can solve the problems of high fermentation cost, and achieve the effects of improving fermentation titer, reducing cost, and low price

Active Publication Date: 2008-10-08
LUNAN BETTER PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, the industrialized production of clavulanic acid has been realized at home and abroad. Soybean flour is mostly used as the main nitrogen source and glycerin is used as the main carbon source. The fermentation cost is relatively high.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Slant culture: Prepare the medium according to the following ratio: glucose 6g / L, malt extract 6g / L, yeast extract 6g / L, agar 23g / L, pH 7.0. Prepare 300 ml of culture medium, heat the agar to melt, stir evenly, put it into 10 large test tubes, sterilize, and make an inclined plane for later use. Dissolve the freeze-dried Streptomyces coryneformis strain with 5 ml sterile water, take 4 ml and evenly spread it on 10 slopes at a temperature of 28° C., a humidity of 40-60%, and cultivate for 11 days to produce a large number of spores. Add sterile water to make a spore suspension.

[0016] Shake bottle seed liquid preparation: Prepare medium according to the following ratio: peptone 7g / L, malt extract 7g / L, yeast extract 7g / L, pH 7.0. Prepare 200 ml of culture medium, fill 4 bottles of 500 ml Erlenmeyer flasks (50 mL per bottle), sterilize and set aside.

[0017] Inoculate 2 mL of the spore suspension into the shake flask. The temperature is 28°C, the humidity is 40-60%, and th...

Embodiment 2

[0021] Slant culture: Prepare the medium according to the following ratio: glucose 8g / L, malt extract 6g / L, yeast extract 4g / L, agar 23g / L, pH 7.3. Prepare 300 ml of culture medium, heat the agar to melt, stir evenly, put it into 10 large test tubes, sterilize, and make an inclined plane for later use. Dissolve the freeze-dried Streptomyces coryneformis strain with 5 ml sterile water, take 4 ml and evenly spread it on 10 slopes at a temperature of 28° C., a humidity of 40-60%, and cultivate for 11 days to produce a large number of spores. Add sterile water to make a spore suspension.

[0022] Shake bottle seed liquid preparation: Prepare medium according to the following ratio: peptone 8g / L, malt extract 8g / L, yeast extract 4g / L, pH 7.2. Prepare 200 ml of culture medium, fill 4 bottles of 500 ml Erlenmeyer flasks (50 mL per bottle), sterilize and set aside. Inoculate 2 mL of the spore suspension into the shake flask. The temperature is 28°C, the humidity is 40-60%, and the culture...

Embodiment 3

[0026] Slant culture: Prepare the medium according to the following ratio: glucose 4g / L, malt extract 4g / L, yeast extract 8g / L, agar 25g / L, pH 6.8. Prepare 300 ml of culture medium, heat the agar to melt, stir evenly, put it into 10 large test tubes, sterilize, and make a slope for later use. Dissolve the freeze-dried Streptomyces coryneformis strain with 5 ml sterile water, take 4 ml and evenly spread it on 10 sloping surfaces at a temperature of 28° C. and a humidity of 40-60%. After culturing for 12 days, a large number of spores will be produced. Add sterile water to make a spore suspension.

[0027] Shake bottle seed liquid preparation: Prepare medium according to the following ratio: peptone 3g / L, malt extract 8g / L, yeast extract 5g / L, pH 6.8. Prepare 200 ml of culture medium, fill 4 bottles of 500 ml Erlenmeyer flasks (50 mL per bottle), sterilize and set aside. Inoculate 2 mL of the spore suspension into the shake flask. The temperature is 28°C, the humidity is 40-60%, and...

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Abstract

The invention belongs to the biomedical field, which relates to a method for producing clavulanic acid through fermentation. Streptomyces clavuligerus are used as original strain in the method, and the method mainly comprises the step of the preparation of slant surface microbial strain, preparation of seed liquid and control of fermentation process. The invention uses cottonseed flour and starch as main nitrogen source and carbon source for fermentation media, through regulating fermentation process, the invention greatly reduces the production cost of the clavulanic acid, the fermentation potency is enhanced, and the deficiencies that the production cost is high and the fermentation potency is low in the prior art are solved.

Description

Technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a new method for fermentative production of clavulanic acid. Background technique [0002] Due to the widespread use of penicillin, certain bacteria have developed resistance to it. Penicillins and cephalosporins both contain a common β-lactam structure and belong to β-lactam antibiotics. When antibiotics with this structure are used, some pathogenic bacteria develop resistance by producing β-lactamase. Clavulanic acid, also known as clavulanic acid, is a β-lactamase inhibitor produced by Streptomyces clavuligerus, which can greatly increase the sensitivity of pathogens to β-lactam antibiotics . Clavulanic acid itself has very weak antibacterial activity, but it is a potent, broad-spectrum and irreversible β-lactamase inhibitor. It can form a firm and irreversible combination with the β-lactamase produced by drug-resistant gram-positive bacteria and gram-negative bacteria in vivo...

Claims

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Application Information

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IPC IPC(8): C12P17/18C12N1/20C12R1/465
Inventor 赵志全
Owner LUNAN BETTER PHARMA
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