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Fermentation method of caspofungin fermentation intermediate

A fermentation method and fermentation process technology, applied in the field of bioengineering, can solve the problems affecting the quality of caspofungin acetate, etc., and achieve the effect of improving the ventilation effect and reducing the viscosity of the bacteria

Active Publication Date: 2017-05-31
BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD +1
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  • Abstract
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  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

C0 impurity can participate in the follow-up reaction, seriously affecting the quality of caspofungin acetate

Method used

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  • Fermentation method of caspofungin fermentation intermediate
  • Fermentation method of caspofungin fermentation intermediate

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Experimental program
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Embodiment 1

[0024] Fermentation strain: Glarea lozoyensis

[0025] Fermentation medium (wt): lactose 3.0%, threonine 1.0%, yeast powder 1.0%, proline 1.2%, KH 2 PO 4 0.15%, magnesium sulfate heptahydrate 0.05%, MES buffer salt 1.5%, pH 5.3.

[0026] 50L fermenter culture, 30L medium, sterilized at 121°C for 30 minutes. The seed volume is 1.5L, the culture temperature of the fermentation broth is 25°C, the initial ventilation volume is 0.9VVM, 200 rpm, and the tank pressure is 0.05Mpa. The maximum amount is 1.2VVM. After 24 hours of fermentation, ammonia water was added to control the pH to 5.0-5.4. After 48 hours of fermentation, start to add vitamin b5, the added amount is 30mg / l. After 60 hours of fermentation, start to feed lactose, the flow rate is 2.0% / day (mass volume ratio), so that the total sugar concentration of the fermentation broth is controlled between 1-3%, until the end of fermentation. After 72 hours of fermentation (at this time, the ventilation rate and rotation s...

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Abstract

The invention relates to a fermentation method of a caspofungin fermentation intermediate and provides a method for reducing content of pneumocandin C0 while increasing the fermentation unit of pneumocandin B0. The strain adopted in the method is glarea lozoyensis. In the invention, a dilute formula is adopted for a culture medium; lactose and ammonia water are fed in the fermentation process, so that the strain viscosity can be effectively lowered, and the ventilation effect is improved; and meanwhile, pH is strictly controlled in the fermentation process. Meanwhile, vitamin b5 is supplemented to fermentation liquid; in the existing fermentation technology of pneumocandin B0, the fermentation unit of pneumocandin B0 is around 800-1,000mg / l; and in the fermentation method provided by the invention, the fermentation unit can be raised to 2,000-2,500mg / l, and the content of pneumocandin C0 is remarkably lowered.

Description

technical field [0001] The invention belongs to the technical field of bioengineering, and relates to microbial fermentation of antifungal drugs, in particular to a microbial fermentation method of pneumocidine B0. Background technique [0002] Echinocandin compounds, discovered in the 1970s, are a class of microbial secondary metabolites with six-membered cyclic peptides and different fatty acid side chains, which can specifically act on fungal cell walls and non-competitively inhibit fungal cell wall β- 1,3-D-glucan synthase activity, which can play an antibacterial effect, and does not affect the human body. Neomercontin B 0 Caspofungin, a semi-synthetic derivative of caspofungin, was the first reported echinocandin compound and was approved by the US FDA in 2001 for the treatment of Aspergillus infection. At present, caspofungin has become the ace drug in the systemic antifungal drug market. [0003] Neomocontin B0 is a secondary metabolite synthesized by fermentation...

Claims

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Application Information

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IPC IPC(8): C12P21/04C12R1/645
CPCC07K7/56
Inventor 袁建栋王其龙别一
Owner BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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