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Fermentation method of micafungin sodium intermediate FR901379

A fermentation method and fermentation liquid technology, applied in the field of microbial fermentation, can solve the problems of reducing production costs, insufficient dissolved oxygen, etc., and achieve the effect of low cost

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

AI Technical Summary

Problems solved by technology

At the same time, simethicone, which is incompatible with the reaction liquid, is introduced into the fermentation broth. In addition to being used as a fermentation precursor, methyl palmitate is also used as an oxygen carrier in the fermentation system together with simethicone to reduce the resistance of gas-liquid oxygen transfer. It solves the problem of insufficient dissolved oxygen in the fermentation process of the prior art, improves the fermentation yield of FR901379, and reduces the production cost

Method used

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  • Fermentation method of micafungin sodium intermediate FR901379

Examples

Experimental program
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Effect test

Embodiment 1

[0019] Transfer the cultured seeds to 30L fermentation medium at 120°C for 30 minutes and cool to 24-26°C at a ratio of 5% (v / v). The composition of the fermentation medium is mass (g) / volume (L ) ratio is: glucose 50, cottonseed cake powder 20, yeast powder 10, peptone 10, magnesium sulfate 2, dipotassium hydrogen phosphate 1, calcium carbonate 4, defoamer 1, and the rest is water.

[0020] During the fermentation process, the temperature is controlled at 24-26°C, the ventilation rate is 1VVM, and the initial rotation speed is 150rpm. During the process, the rotation speed is adjusted between 150-600rpm so that the dissolved oxygen is not lower than 20%.

[0021] Methyl palmitate and simethicone are formulated into a solution according to the mass volume ratio of simethicone at 10% and sterilized at 120° C. for 30 minutes before use.

[0022] After 48 hours of fermentation, a mixture of methyl palmitate and simethicone was added to the fermentation broth at a mass volume rati...

Embodiment 2

[0025] Transfer the cultured seeds to 30L fermentation medium at 120°C for 30 minutes and cool to 24-26°C at a ratio of 5% (v / v). The composition of the fermentation medium is mass (g) / volume (L ) ratio is: glucose 50, cottonseed cake powder 20, yeast powder 10, peptone 10, magnesium sulfate 2, dipotassium hydrogen phosphate 1, calcium carbonate 4, defoamer 1, and the rest is water.

[0026] During the fermentation process, the temperature is controlled at 24-26°C, the ventilation rate is 1VVM, and the initial rotation speed is 150rpm. During the process, the rotation speed is adjusted between 150-600rpm so that the dissolved oxygen is not lower than 20%.

[0027] Methyl palmitate and simethicone are formulated into a solution according to the mass volume ratio of simethicone at 5% and sterilized at 120° C. for 30 minutes before use.

[0028] After 48 hours of fermentation and cultivation, a mixture of methyl palmitate and simethicone oil in a mass volume ratio of 10% was adde...

Embodiment 3

[0031] Transfer the cultured seeds to 30L fermentation medium at 120°C for 30 minutes and cool to 24-26°C at a ratio of 5% (v / v). The composition of the fermentation medium is mass (g) / volume (L ) ratio is: glucose 50, cottonseed cake powder 20, yeast powder 10, peptone 10, magnesium sulfate 2, dipotassium hydrogen phosphate 1, calcium carbonate 4, defoamer 1, and the rest is water.

[0032] During the fermentation process, the temperature is controlled at 24-26°C, the ventilation rate is 1VVM, and the initial rotation speed is 150rpm. During the process, the rotation speed is adjusted between 150-600rpm so that the dissolved oxygen is not lower than 20%.

[0033] Methyl palmitate and simethicone are formulated into a solution according to the mass volume ratio of simethicone at 8% and sterilized at 120° C. for 30 minutes before use.

[0034] After 48 hours of fermentation and cultivation, a mixture of methyl palmitate and simethicone in a mass volume ratio of 8% was added to ...

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Abstract

The invention discloses a brand-new fermentation method of FR901379. According to the method, methyl palmitate is added as a side chain precursor of FR901379 fatty acid in the fermentation process ofFR901379 so as to promote biosynthesis of FR901379. At the same time, dimethyl silicone oil insoluble in a reaction solution is introduced into a fermentation broth. Besides serving as a fermentationprecursor, methyl palmitate also serves as an oxygen carrier in the fermentation system together with methyl silicone oil, so that resistance of gas-liquid oxygen transfer is reduced, the problem of insufficient dissolved oxygen in the fermentation process in the prior art is solved, the fermentation yield of FR901379 is increased, and the production cost is reduced.

Description

technical field [0001] The invention relates to the field of microbial fermentation, in particular to the preparation of an antifungal fermented semi-synthetic drug precursor, and more specifically to a fermentation method for micafungin sodium intermediate FR901379. Background technique [0002] In recent years, due to the increasing number of immunocompromised patients, the incidence of fungal infections has increased significantly, especially the incidence and mortality of deep fungal infections. Echinocandin antibiotics are a group of natural products discovered in the 1970s, with similar cyclic polypeptide cores and different fatty acid side chains, which can non-competitively inhibit fungal cell wall β-1,3-glucan synthesis Enzyme activity, so as to achieve the purpose of antifungal. Compared with traditional antifungal drugs, this type of drug has a unique mechanism of action, low toxicity and side effects, and has strong antibacterial activity against some azole and ...

Claims

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Application Information

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IPC IPC(8): C12P21/02C12R1/645
CPCC12P21/02
Inventor 袁建栋别一
Owner BRIGHTGENE BIO MEDICAL TECH (SUZHOU) CO LTD
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