Medium for fermentation production of FR901379 and method thereof

A FR901379, fermentation culture technology, applied in the direction of microorganism-based methods, biochemical equipment and methods, fermentation, etc., can solve the problems of FR901379 low fermentation unit, low dissolved oxygen, high viscosity of fermentation broth, etc.

Active Publication Date: 2018-05-29
CHONGQING QIANTAI BIOLOGICAL MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the current fermentation production technology of FR901379, due to the growth characteristics of filamentous bacteria in the fermentation broth, the viscosity of the fermentation broth is too high, the oxygen transfer effect is poor, and the dissolved oxygen is low, thereby inhibiting the secondary metabolism of the bacteria, resulting in FR901379 low fermentation unit

Method used

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  • Medium for fermentation production of FR901379 and method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Transfer 3% of the cultured seeds into 30L fermentation medium sterilized at 120°C for 30 minutes and then cooled to 24-26°C. The composition of the fermentation medium, the mass (g) / volume (L) ratio is: fructose 130. Corn gluten powder 17, casein 8, yeast peptone 8, magnesium sulfate 2, dipotassium hydrogen phosphate 0.75, calcium carbonate 3, defoamer 1, and the rest is water.

[0031] During the fermentation process, the temperature is 24-26°C, the ventilation volume is 1VVM, and the initial rotation speed is 150rpm. During the process, the rotation speed is adjusted between 150 and 600rpm so that the dissolved oxygen is not lower than 20%.

[0032] The fructose was prepared into a 500g / L aqueous solution and sterilized at 120°C for 30 minutes before use, and diluted with hydrogen peroxide to a 30% aqueous solution for use. Fermentation starts at 90 hours, and fructose and hydrogen peroxide are added to the fermenter respectively. The method of addition is continuous...

Embodiment 2

[0034] Transfer the cultured seeds to 300L fermentation medium at 120°C for 30 minutes and then cool to 24-26°C at a ratio of 3%. The composition of the fermentation medium is as follows: fructose 140. Corn gluten powder 15, casein 7.5, yeast peptone 9, magnesium sulfate 2, dipotassium hydrogen phosphate 0.8, calcium carbonate 3, defoamer 1, and the rest is water.

[0035] During the fermentation process, the temperature is 24-26°C, the ventilation rate is 1VVM, and the initial speed is 80rpm. During the process, the speed is adjusted between 80~250rpm so that the dissolved oxygen is not lower than 20%.

[0036] The fructose was prepared into a 500g / L aqueous solution and sterilized at 120°C for 30 minutes before use, and diluted with hydrogen peroxide to a 30% aqueous solution for use. Fermentation starts at 80 hours, and fructose and hydrogen peroxide are added to the fermenter respectively. The method of addition is continuous and uninterrupted, and the addition is stopped ...

Embodiment 3

[0038] Transfer the cultured seeds into 3000L fermentation medium at 120°C for 30 minutes and cool to 24-26°C at a ratio of 2.5%. The composition of the fermentation medium is: mass (g) / volume (L) ratio: fructose 150, corn gluten powder 20, casein 7.5, yeast peptone 5, magnesium sulfate 2, dipotassium hydrogen phosphate 0.6, calcium carbonate 3, defoamer 0.7, and the rest is water.

[0039] During the fermentation process, the temperature is 24-26°C, the ventilation rate is 1VVM, and the initial speed is 60rpm. During the process, the speed is adjusted between 60 and 200rpm so that the dissolved oxygen is not lower than 20%.

[0040] The fructose was prepared into a 500g / L aqueous solution and sterilized at 120°C for 30 minutes before use, and diluted with hydrogen peroxide to a 30% aqueous solution for use. Fermentation starts at 76 hours, and fructose and hydrogen peroxide are added to the fermenter respectively. The method of addition is continuous and uninterrupted, and th...

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Abstract

The invention provides a medium for fermentation production of FR901379 and a method thereof. The medium comprises the following components in parts by mass: 120-160 parts of fructose, 10-20 parts ofcorn gluten meal, 5-10 parts of casein, 5-10 parts of yeast peptone, 1-3 parts of magnesium sulfate, 0.5-1 part of dipotassium hydrogen phosphate, 2-4 parts of calcium carbonate, and 0.5-1 part of anantifoaming agent. The invention also provides a method for culturing a bacterial strain Coleophoma empetri in the medium to obtain FR901379. The fermentation medium and the produced FR901379 can obviously reduce the broth consistency, improves oxygen dissolving condition during a fermentation process, promotes the thalline secondary metabolism, and obviously increased the output of FR901379.

Description

technical field [0001] The invention relates to the field of microbial fermentation, in particular to a fermentation medium and a method for producing an intermediate FR901379 of the echinocandin antifungal drug micafungin. Background technique [0002] Echinocandins are new antifungal drugs that have been listed in recent years, which can inhibit the β-1,3-D-glucose synthase in the fungal cell wall, because mammalian cells lack β-1,3-D-glucose synthase , so this type of compound has high specificity to fungal cells, can quickly kill fungi and has little effect on normal human cells, so it has good curative effect and high safety. Such drugs currently on the market are: caspofungin, micafungin and anidifungin. [0003] FR901379 is a fermentation product of the strain Coleophoma empetri. Through a series of structural modifications to FR901379, the echinocandin antifungal drug Micafungin (Micafungin) can be obtained. [0004] Micafungin was developed by Fujisawa Corporatio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P21/04C12R1/645
CPCC07K7/56C12P21/02
Inventor 别一王其龙刘省伟
Owner CHONGQING QIANTAI BIOLOGICAL MEDICINE
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