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Novel preparation method of micafungin sodium precursor

A polymer, FR901379 technology, applied in the fermentation field of micafungin sodium precursor FR179642, can solve the problems of complicated separation and purification steps, slow conversion speed, poor stability, etc., and achieves simple operation, high conversion rate and low cost. Effect

Inactive Publication Date: 2018-11-06
BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] Chinese patent CN106544382 discloses a method for converting FR901379 into FR179642. This method significantly improves the conversion efficiency of the enzyme by controlling the initial concentration of FR901379 in the conversion liquid and controlling the temperature and pH during the conversion process, and the conversion rate can be as high as 83%. , but the method disclosed in this patent is to collect bacteria for transformation. There are a large number of microorganisms in the transformation system, the transformation speed is slow, the stability of the enzyme is poor, the separation and purification steps are complicated, and the cost is high
[0018] The enzymes used in the currently reported cross-linked enzyme polymers include hydrolases, lyases, and oxidoreductases. At present, there are no reports on the fermentation of semi-synthetic drugs, and there are no reports on the application of this technology to deacylases.

Method used

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Effect test

Embodiment 1

[0042] The cultivated seeds were transferred to a 30L fermentation medium at a ratio of 5% (v / v) at 120°C for 30 minutes and then cooled to 24-26°C. The fermentation medium was composed of mass (g) / volume (L The ratio is: glucose 50, cottonseed meal powder 20, yeast powder 10, peptone 10, magnesium sulfate 2, dipotassium hydrogen phosphate 1, calcium carbonate 4, antifoaming agent 1, and the rest is water.

[0043] During the fermentation process, the temperature is controlled at 24-26°C, the aeration rate is 1VVM, and the initial rotation speed is 150rpm. During the fermentation process, the rotation speed is adjusted between 150 and 600rpm so that the dissolved oxygen is not less than 20%.

[0044] Methyl palmitate and dimethicone were prepared into a solution according to the mass-volume ratio of dimethicone at 10%, and then sterilized at 120°C for 30 minutes for use.

[0045] After 48 hours of fermentation and cultivation, 3% of the mixture of methyl palmitate and simethicone was...

Embodiment 2

[0048] The cultivated seeds were transferred to a 30L fermentation medium at a ratio of 5% (v / v) at 120°C for 30 minutes and then cooled to 24-26°C. The fermentation medium was composed of mass (g) / volume (L The ratio is: glucose 50, cottonseed meal powder 20, yeast powder 10, peptone 10, magnesium sulfate 2, dipotassium hydrogen phosphate 1, calcium carbonate 4, antifoaming agent 1, and the rest is water.

[0049] During the fermentation process, the temperature is controlled at 24-26°C, the aeration rate is 1VVM, and the initial rotation speed is 150rpm. During the fermentation process, the rotation speed is adjusted between 150 and 600rpm so that the dissolved oxygen is not less than 20%.

[0050] Methyl palmitate and dimethicone were prepared into a solution according to the mass-volume ratio of dimethicone of 5%, and then sterilized at 120°C for 30 minutes for use.

[0051] After 48 hours of fermentation and cultivation, a 10% mass volume ratio of methyl palmitate and simethicon...

Embodiment 3

[0054] The cultivated seeds were transferred to a 30L fermentation medium at a ratio of 5% (v / v) at 120°C for 30 minutes and then cooled to 24-26°C. The fermentation medium was composed of mass (g) / volume (L The ratio is: glucose 50, cottonseed meal powder 20, yeast powder 10, peptone 10, magnesium sulfate 2, dipotassium hydrogen phosphate 1, calcium carbonate 4, antifoaming agent 1, and the rest is water.

[0055] During the fermentation process, the temperature is controlled at 24-26°C, the aeration rate is 1VVM, and the initial rotation speed is 150rpm. During the fermentation process, the rotation speed is adjusted between 150 and 600rpm so that the dissolved oxygen is not less than 20%.

[0056] Methyl palmitate and dimethicone were prepared into a solution according to the mass-volume ratio of dimethicone of 8%, and then sterilized at 120°C for 30 minutes for use.

[0057] After 48 hours of fermentation and cultivation, the fermentation broth was supplemented with a mixture of ...

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Abstract

The invention discloses a preparation method of FR179642. The method comprises the following steps: 1) preparing a medium for fermenting FR901379; 2) inoculating a fermentation medium with a bacterialstrain Coleophoma empetri seed culture solution for fermentation; 3) supplementing a mixture of methyl palmitate and dimethicone to a fermentation broth after fermentation culture for 24-72 h; 4) finishing fermentation when the concentration of FR901379 no longer increases after fermentation for 160 h; 5) enabling FR901379 obtained in the previous step to be subjected to a reaction with a deacylase cross-linked enzyme polymer to be converted into FR179642.

Description

Technical field [0001] The present invention relates to the field of microbial fermentation, in particular to the preparation of antifungal fermented semi-synthetic drug precursors, and more specifically to a fermentation method of micafungin sodium precursor FR179642. Background technique [0002] In recent years, due to the increase in immunocompromised patients year by year, the incidence of fungal infections has increased significantly, especially the incidence and mortality of deep fungal infections. Echinocandins antibiotics are a group of natural products discovered in the 1970s. They have similar cyclic polypeptide cores and different fatty acid side chains, and can non-competitively inhibit the synthesis of fungal cell wall β-1,3-glucan Enzyme activity, so as to achieve the purpose of anti-fungal. Compared with traditional antifungal drugs, this class of drugs has a unique mechanism of action, low toxic and side effects, and has strong antibacterial activity against som...

Claims

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Application Information

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IPC IPC(8): C12P21/04C12R1/47
CPCC07K7/56C12P21/02
Inventor 袁建栋别一
Owner BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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