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Fermentation production method of fidaxomicin

A technology of fidaxomicin and fermentation broth, which is applied in the field of microbial fermentation to produce antibiotics, can solve the problems of lack of delayed carbon and nitrogen sources in the medium, low yield of fermentation products, poor fermentation effect, etc., and achieves increasing the utilization rate of the medium , the effect of improving fermentation yield and mild conditions

Active Publication Date: 2015-04-29
CHONGQING QIANTAI BIOLOGICAL MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Part of the fermentation process in CA1040564, GB1458512, and US3978211 is too simplified, and the medium lacks slow-acting carbon and nitrogen sources, resulting in poor fermentation results
U.S. Patent US20100028970 mentions the relevant carbon and nitrogen sources and trace elements of fermentation, and involves the use of a medium containing glucose, inorganic salts, amino acids and yeast extracts in the fermentation process, but the above-mentioned fermentation method still has complex operations, and the yield of fermentation products is high. The problem of low yield, as the demand for antibiotics in the global market is not only increasing, so there is a need for improved methods that can significantly increase the effectiveness of fermented units of fidaxomicin

Method used

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  • Fermentation production method of fidaxomicin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Batch-type addition of edible oil during fermentation

[0030] Prepare 300L seed medium in a 500L seed tank, sterilize at 120°C for 30 minutes, cool to 27°C, inoculate 48h seed-age shake flask seeds at an inoculum volume ratio of 0.1% of the seed medium volume, and incubate at 27°C for 28h.

[0031] Prepare 3500L fermentation medium in a 5000L fermenter, sterilize at 120°C for 30 minutes, then cool to 27°C, insert the vegetative inoculum into the above seed medium with an inoculation amount of 4% by volume of the fermentation medium, and control the temperature during the fermentation process The temperature is 27°C, the control pressure is 0.04Mpa, the control ventilation is 0.5VVM, and the control speed is 100rpm to ensure that the dissolved oxygen is above 30%.

[0032] The fermentation culture is continued, and after 48 hours, the dissolved oxygen in the fermenter drops to 32%, and gradually begins to rise again, and soybean oil is added to the fermenter...

Embodiment 2

[0033] Example 2 Continuous Addition of Edible Oil During Fermentation

[0034] Prepare 100L seed medium in a 200L seed tank, sterilize at 120°C for 30 minutes, cool to 27-29°C, insert 48h seed-age shake flask seeds at an inoculum volume ratio of 0.3% of the seed medium volume, and then incubate at 29°C for 36h .

[0035] Prepare 1400L fermentation medium in a 2000L fermenter, sterilize at 120°C for 30 minutes and then cool to 29°C, add the vegetative inoculum in the above seed medium according to the inoculum volume ratio of 8% of the fermentation medium volume, and control the temperature during the fermentation process The temperature is 29°C, the control pressure is 0.06Mpa, the control ventilation is 1.5VVM, and the control speed is 250rpm to ensure that the dissolved oxygen is above 30%.

[0036] Continue the fermentation culture. After 64 hours, the dissolved oxygen in the fermenter drops to 33%, and gradually starts to rise again. Take 24 hours as a time unit, and b...

Embodiment 3

[0037] Example 3 Adding edible oil intermittently during the fermentation process

[0038] Prepare 100L seed medium in a 200L seed tank, sterilize at 120°C for 30 minutes, then cool to 28°C, inoculate 48h-old shake flask seeds at an inoculum volume ratio of 0.2% of the seed medium volume, and then incubate at 28°C for 30h.

[0039] Prepare 700L fermentation medium in a 1000L fermenter, sterilize at 120°C for 30 minutes and then cool to 28°C, insert the vegetative inoculum into the above seed medium with an inoculation amount of 5% by volume of the fermentation medium, and control the temperature during the fermentation process At 28°C, control the pressure at 0.05Mpa, control the ventilation at 1.0VVM, and control the speed at 200rpm to ensure that the dissolved oxygen is above 30%.

[0040]The fermentation culture is continued, and the dissolved oxygen in the fermenter drops to 30% after 52 hours, and gradually begins to rise again. Add rapeseed oil to the fermenter every t...

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Abstract

The invention discloses a fermentation production method of fidaxomicin. In the fermentation production process of fidaxomicin, edible oil is added to a fermentation liquid, and the productivity of target products is improved; when dissolved oxygen of the fermentation liquid starts to rise from the lowest point, edible oil is intermittently or continuously added. According to the method, the operation is simple, the condition is mild, the raw material source is wide, the equipment requirement is low, the production cost is reduced, the fermentation yield is greatly increased, and the method is suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of microbial fermentative production of antibiotics, in particular to the fermentative production of fidaxomicin. Background technique [0002] Fidaxomicin is a new type of narrow-spectrum macrolide antibiotics developed by Optimer, the trade name is Dificid, mainly used for the treatment of Clostridium difficile-associated diarrhea (CDAD), released in May 2011 On the 27th, it was approved for marketing by the FDA. Compared with metronidazole and vancomycin, the current main treatment drugs, fidaxomicin can significantly reduce the recurrence rate. The structural formula of Fidaxomycin is as follows: [0003] [0004] The preparation of fidaxomicin is mainly produced by the fermentation process of the actinomycete Dactylosporangium aurantiacum. At present, there are few reports on the fermentation process of fidaxomicin at home and abroad. Part of the fermentation process in CA1040564, GB1458512, and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/62C12R1/01
Inventor 别一罗永莎唐恒袁建栋
Owner CHONGQING QIANTAI BIOLOGICAL MEDICINE
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