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Fermentation medium and fed batch method for improving fermentation level of meleumycin

A technology of meleomycin and culture medium, which is applied in the field of fermentation medium and feeding material to improve the fermentation level of mebemycin, can solve the problems of kitasamycin stagflation, metabolic pH increase, bacterial autolysis, etc. To achieve the effect of reducing risk

Active Publication Date: 2018-05-22
PEKING UNIV FOUNDER GRP CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The present invention aims to solve the problem of stagflation of kitasamycin and autolysis of bacteria caused by the increase of metabolic pH accompanied by insufficient dissolved oxygen in the existing Maibamycin fermentation production process, and provides a method for improving the production of Maibelamycin. Feed method for vegetarian fermentation level

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 is used to improve the feeding method of mebamycin fermentation level

[0024] The medium for fermenting mebamycin provided in this example contains the following components: 2% glucose, 4% soybean powder, 0.2% yeast powder, 0.4% fish meal, 0.1% potassium dihydrogen phosphate, 0.1% magnesium sulfate and corn Oil 8%. The fermentation method is as follows:

[0025] 1. Preparation of seed solution: insert Streptomyces mikaii into the solid slant medium No. 1 of Gaoshi, and cultivate it at 28°C for 5 days; In the bottle, the liquid volume is 100mL / 750mL, at 28°C, the stirring speed is 220rpm, and the shaking is cultivated for 30 hours to obtain the seed liquid. The amount of viable bacteria in the obtained seed liquid was about 6×10 7 CFU / mL.

[0026] The formula of the liquid seed medium is: 1% of glucose, 2% of starch, 3% of soybean powder, 0.03% of potassium dihydrogen phosphate, 0.3% of ammonium sulfate and 0.2% of calcium carbonate.

[0027] 2, the fe...

Embodiment 2

[0030] Embodiment 2 is used to improve the feeding method of mebamycin fermentation level

[0031] The medium for fermenting mebamycin provided in this example contains the following components: 1.5% glucose, 5% soybean powder, 0.1% yeast powder, 0.5% fish meal, 0.05% potassium dihydrogen phosphate, 0.2% magnesium sulfate and corn Oil 1%.

[0032] The fermentation method is the same as described in Example 1. When the pH value of the fermented liquid bounces back to 6.0 from the lowest point, 3L of glucose solution with a concentration of 3% is added at one time, the flow acceleration rate is 200ml / h, and the fermentation period is 5 days. After the fermentation is finished, put the tank, the pH of the fermented liquid is 5.82, and the volume of the tank is 30L.

[0033] In this example, the content of mebelamycin is 3410 mg / L, the weight ratio of midecamycin A1 to mebelamycin is 58.35%, and the weight ratio of kitasamycin A6 to mebelamycin is 25.46%. The volume of mebelamyc...

Embodiment 3

[0034] Embodiment 3 is used to improve the feeding method of mebelamycin fermentation level

[0035] The medium for fermenting mebamycin provided in this example contains the following components: 3% glucose, 2% soybean powder, 0.3% yeast powder, 0.1% fish meal, 0.2% potassium dihydrogen phosphate, 0.05% magnesium sulfate and corn Oil 10%.

[0036] The fermentation method is the same as that described in Example 1. When the pH value of the fermented liquid bounced back to 6.0 from the lowest point, 0.6L of 15% glucose solution was added in one flow, the flow rate was 200ml / h, and the fermentation period was 8 days. After the fermentation is finished, put the tank, the pH of the fermented liquid is 5.58, and the volume of the tank is 27.6L.

[0037] In this example, the content of mebelamycin is 3720 mg / L, the weight ratio of midecamycin A1 to mebelamycin is 58.78%, and the weight ratio of kitamycin A6 to mebelamycin is 24.72%. The volume of mebelamycin produced by fermentation...

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Abstract

The invention provides a fermentation medium for improving the fermentation level of meleummycin. The fermentation medium includes 1.5-3.0% of glucose, 2-5% of soybean powder, 0.1-0.3% of yeast powder, 0.1-0.5% of fish meal, 0.05-0.2% of potassium dihydrogen phosphate, 0.05-0.2% of magnesium sulfate and 1-10% of oil. The invention also provides a method for improving the fermentation level of meleomycin. The medium is used, Streptomyces mycarofaciens is used as a fermentation strain, and a glucose solution is added when the pH of a fermentation broth rebounds to 6.0 from the lowest point in order to improve the fermentation level of meleomycin and the proportion of kitasamycin. The method is simple and is easy to implement, and when the method is used for the fermentative production of meleummycin, the content of the meleummycin can reach 3400-4000 mg / L, the weight proportion of medemycin A1 is about 58.38-59.75%, and the weight proportion of kitasamycin A6 can reach 24.72-29.72%; andthe tank yield of meleomycin after fermentation is about 1.2 times more than that of a control group without a supplemental glucose solution, and the A6 component content is increased by about 25% ormore.

Description

technical field [0001] The invention relates to the technical field of microbial fermentation and biopharmaceuticals, in particular to a fermentation medium and feeding method for improving the fermentation level of mebelamycin. Background technique [0002] Meleumycin (Meleumycin, MLM) is obtained from Streptomyces (S. mycarofaciens 10204 and 1748) isolated from the soil of Sichuan and Guangdong by Chinese researchers, and refined through fermentation. Mebemycin has good antibacterial effect on erythromycin-sensitive bacteria in Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes and pneumococcus, and other common clinical symptoms such as Streptococcus parvum and Neisseria gonorrhoeae Pathogenic bacteria have certain antibacterial activity. [0003] The requirement for midecamycin in the 2005 edition of Pharmacopoeia is that the content of midecamycin A1 should not be less than 35.0%. With the revision of the Pharmacopoeia, the requirements for mebe...

Claims

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Application Information

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IPC IPC(8): C12P19/62C12R1/465
CPCC12N1/20C12P19/62
Inventor 吴峰张葵周镪
Owner PEKING UNIV FOUNDER GRP CO LTD
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