Fermentation culture medium and fermentation method for producing pentostatin by fermentation of streptomyces antibioticus

A fermentation medium and anti-streptomyces technology, applied in the field of industrial microorganisms, can solve the problem of low fermentation units of pentostatin, and achieve the effect of increasing production and increasing fermentation units

Inactive Publication Date: 2014-03-26
SHANGHAI INST OF PHARMA IND CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Therefore, the technical problem to be solved in the present invention is to provide a new fermentation medium and corresponding The fermentation method can greatly increase the fermentation unit of pentostatin and improve production efficiency

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Streptomyces antibioticus NRRL3238 (purchased from the US Department of Agriculture Culture Collection) was streaked on the seed slant medium, cultured at 28°C for 7 days, and then inoculated into the seed medium with a loading volume of 20ml / 250ml. ℃, 250rpm rotary shaker for 36h. The obtained fermented seeds were inoculated in a 5L fermenter containing 2L medium with a 1% (v / v) inoculation amount, the fermentation temperature was automatically controlled to 30°C, pH 6.5, the speed was related to dissolved oxygen, and the dissolved oxygen was maintained at 40 %, ventilation volume 0.5VVM. At 24h, start to feed glucose 1-10‰L / h, and the fermentation period is 72h. The output of pentostatin reaches 50mg / L.

[0031] The slant medium used therein consists of: glucose 4.0g / L, yeast extract powder 4.0g / L, malt extract powder 10.0g / L, agar powder, 20.0g / L, pH natural.

[0032] The composition of the seed medium used: 2% glucose, 2% soybean cake powder, 0.5% NaCl, 0.25% CaC...

Embodiment 2

[0035] The 1% (v / v) inoculum of the seeds prepared in Example 1 was inoculated in the fermentation medium for fermentation. Fermentation medium composition: glucose 10.0g / L, fine bean dregs 30.0g / L, yeast extract powder 5.0g / L, NaCl 5.0g / L. Automatically control the fermentation temperature to 30°C, pH to 6.5, dissolved oxygen to 40%, ventilation to 0.5VVM, and start to feed glucose at 1 to 10‰L / h every 24 hours. The fermentation period was 72h, and the output of pentostatin reached 20mg / L.

Embodiment 3

[0037] The 1% (v / v) inoculum of the seeds prepared in Example 1 was inoculated in the fermentation medium for fermentation. Fermentation medium composition: glucose 60.0g / L, fine bean dregs 30.0g / L, yeast extract powder 5.0g / L, NaCl 5.0g / L. Automatically control the fermentation temperature to 30°C, pH to 6.5, dissolved oxygen to 40%, ventilation to 0.5VVM, and start to feed glucose at 1 to 10‰L / h every 24 hours. The fermentation period was 72h, and the output of pentostatin reached 30mg / L.

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Abstract

The invention provides a fermentation culture medium and a fermentation method for producing pentostatin by fermentation of streptomyces antibioticus. The fermentation culture medium comprises a carbon source and a nitrogen source, wherein based on the total weight of the culture medium, the content of the carbon source is 0.5-14%, and the content of the nitrogen source is 0.5-10%; and the carbon source is one or more of glucose, dextrin and wheat starch, and the nitrogen source is one or more of fine bean pulp powder, soy protein, soybean cake powder, yeast soaking powder and cotton seed cake powder. According to the invention, the yield of pentostatin is greatly improved through optimizing the fermentation parameters of the fermentation culture medium, such as components and proportioning of the carbon and nitrogen sources, culture temperature, pH and the like. By using the fermentation production method of pentostatin, the fermentation unit of pentostatin is greatly improved, and the fermentation method is suitable for large scale production of pentostatin.

Description

technical field [0001] The invention belongs to the technical field of industrial microorganisms, and in particular relates to a novel fermentation medium for producing pentostatin by fermentation of antibiotic streptomyces and a corresponding fermentation method. Background technique [0002] In 1974, Woo et al. from Warner Lambert Company discovered an adenosine deaminase inhibitor-pentostatin from the fermentation broth of Streptomyces antibioticus. In 1992, pentostatin was approved by the FDA for the treatment of stem cell leukemia (hairy cell leukemia, HCL). With the increase of its clinical application, the market demand increases. However, there are very few reports on the production of pentostatin. The only reported fermentation process is found in US3923785. In this patent, Streptomyces NRRL3238 is used as the production strain, and a relatively simple culture medium and culture method are mainly reported. , the purpose of which is to isolate pentostatin from the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P19/38C12R1/48
Inventor 陈少欣王岩杨鹏
Owner SHANGHAI INST OF PHARMA IND CO LTD
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