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A kind of fermentation process of mycophenolic acid

A fermentation process, mycophenolic acid technology, applied in the direction of fermentation, microorganism-based methods, microorganisms, etc., can solve problems such as easy to leak tanks, easy to infect bacteria, and large foam production, so as to promote the generation of metabolites and improve Fermentation level, effect of promoting mycelia growth

Active Publication Date: 2020-12-04
GUANGDONG BLUE TREASURE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Lou Xin et al. used response surface analysis to optimize mycophenolic acid fermentation medium, but there was no industrial application, nor did they disclose that the fermentation level could be achieved.
[0005] In addition, due to the characteristics of the culture medium and mycophenolic acid-producing bacteria, the production process of mycophenolic acid fermentation usually has a large amount of foam, which is easy to leak into the tank, and there is a risk of easy bacterial contamination, and the high amount of foam cannot increase the amount of fermentation tank. volume, which further limits the output of tanks
Although the addition of antifoaming agent can well control the foam in the fermenter, it will affect the downstream extraction and purification of mycophenolic acid due to the use of antifoaming agent, resulting in difficult operations such as fermentation broth filtration, extraction crystallization and low yield.
Existing technology does not provide a better solution

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Embodiment 1, a kind of fermentation process of mycophenolic acid

[0035] S1 Culture the slant of the bacterial strain inoculated with Penicillium brevismi at 28° C. for 9 days, add 10 ml of 30% glycerol, wash the spores, shake well, get 7 ml and put them in the glycerol oil tube to obtain glycerol spores;

[0036] S2 sucks the glycerol spores that step S1 makes and places it in the seed culture medium to cultivate, and the described seed culture medium prepares 23L of the seed culture medium according to the following formula with a 50L seed tank: glucose 85g / L, yeast powder 15g / L, peptone 15g / L, K 2 HPO 4 ·3H 2 O 1g / L, MgSO 4 ·7H 2 O 0.4g / L, GPE antifoaming agent 1.4g / L, adjust pH4.2, at 30℃, air flow is 0.5m 3 / h, the pressure of the culture tank is 0.03Mpa, and the stirring speed is cultivated for 50h under the condition of 400rpm to obtain the seed bacteria;

[0037] S3 inserts the seed bacterium that step S2 obtains into fermentation medium by 10% inoculum ...

Embodiment 2

[0038] Embodiment 2, a kind of fermentation process of mycophenolic acid

[0039] S1 Cultivate the slant of the bacterial strain inoculated with Penicillium brevismi at 28° C. for 10 days, add 10 ml of 30% glycerol, wash the spores, shake well, get 7 ml and put them in a glycerin oil tube to obtain glycerol spores;

[0040] S2 sucks the glycerol spores that step S1 makes and places it in the seed medium for cultivation, and the described seed medium prepares 23L of the seed medium with a 50L seed tank according to the following formula: glucose 90g / L, yeast powder 20g / L, peptone 17g / L, K 2 HPO 4 ·3H 2 O 2g / L, MgSO 4 ·7H 2 O 0.5g / L, GPE antifoaming agent 1.8g / L, adjust the pH to 4.2, at 30°C, the air flow is about 0.5m 3 / h, the pressure of the culture tank is 0.03Mpa, and the stirring speed is cultivated for 50h under the condition of 400rpm to obtain the seed bacteria;

[0041] S3 inserts the seed bacterium that step S2 obtains into the fermentation medium by 10% inocul...

Embodiment 3

[0042] Embodiment 3, a kind of fermentation process of mycophenolic acid

[0043] S1 Culture the slant of the bacterial strain inoculated with Penicillium brevismi at 28° C. for 9 days, add 10 ml of 30% glycerol, wash the spores, shake well, get 7 ml and put them in the glycerol oil tube to obtain glycerol spores;

[0044] S2 draws the glycerol spores that step S1 makes and places it in the seed culture medium to cultivate, and the described seed culture medium prepares 23L of the seed culture medium according to the following formula with a 50L seed tank: glucose 95g / L, yeast powder 25g / L, peptone 18g / L, K 2 HPO 4 ·3H 2 O 3g / L, MgSO 4 ·7H 2 O 0.6g / L, GPE antifoaming agent 1.8g / L, adjust the pH to 4.2, at 30°C, the air flow is about 0.5m 3 / h, the pressure of the culture tank is 0.03Mpa, and the stirring speed is cultivated for 50h under the condition of 400rpm to obtain the seed bacteria;

[0045] S3 inserts the seed bacterium that step S2 obtains and cultivates in the ...

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Abstract

The invention belongs to the technical field of microbial fermentation, and in particular relates to a fermentation process of mycophenolic acid. The fermentation process comprises preparing the glycerol spores by penicillium brevicompactum, then performing seed culture and fermentation culture and timely supplementing glucose and glycine in the fermentation liquid during the fermentation culture.According to the fermentation process, sunflower seed cake powder is added to a fermentation medium, which can not only reduce the dosage of an antifoaming agent, but also promote the growth of mycelium and promote the formation of metabolites. At the same time, a glycine solution can be supplemented by the program addition method in the fermentation process, so that the concentration of the glycine in the fermentation liquid can be maintained within a suitable range, the production of the metabolites can be continuously promoted, and the influence of the excessive concentration in the initial medium on the produced bacteria can be avoided. The process can effectively improve the fermentation level of the penicillium brevicompactum and increase the yield of the mycophenolic acid.

Description

technical field [0001] The invention belongs to the technical field of microbial fermentation, and in particular relates to a fermentation process of mycophenolic acid. Background technique [0002] Mycophenolic acid (Mycophenolic Acid, MPA, also known as mycophenolic acid) is an antibiotic with antifungal, antitumor and immunosuppressive effects produced by Penicillium brevis The hypoxanthine mononucleotide dehydrogenase (MPDH) inhibitor can inhibit the initial synthesis pathway of guanine nucleotides, deplete guanine nucleotides, and block DNA synthesis. Clinically, it is often used in the form of mycophenolate mofetil (MMF) and mycophenolate sodium (MPS). The production method of mycophenolic acid has two ways: chemical synthesis and biosynthesis. The chemical synthesis method is difficult to industrialize due to many steps and low yield. The large-scale production in the world uses the fermentation production method of Penicillium microorganisms to prepare mycophenolic ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/04C12R1/80
Inventor 熊志刘任民黄秀芳
Owner GUANGDONG BLUE TREASURE PHARMA
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