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Method for producing Daptomycin by fed-batch decyl aldehyde fermentation

A technology of daptomycin and stream-added decanal, applied in the field of stream-added decanal fermentation production of daptomycin, can solve the problems of adding decanal solution and the like, and achieve the effect of ensuring the effect

Inactive Publication Date: 2014-04-02
CHENGDU YATU BIOLOGICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] So far, there has been no report on the addition of decanal solution during feeding

Method used

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Embodiment 1

[0015] A method for producing daptomycin by fed-batch decanal fermentation, comprising the following:

[0016] a. Cultivate Streptomyces roseospora seed liquid;

[0017] b. Inoculation: inoculate the seed solution obtained in step a into the fermentation medium;

[0018] c. Fermentation culture: the inoculated medium obtained in step b is cultivated and fermented, and the fermentation temperature is 30-32°C;

[0019] d. Add decanal solution: After 18 hours of fermentation, add decanal solution with a mass concentration of 6.0% (the solvent is a mixture of ethanol and water) to the fermentation broth. The feeding speed is: Feed to the fermenter at a flow rate of 1.0-2.0ml / h until the end of fermentation;

[0020] e. Finishing of fermentation and separation: After 48-168 hours of fermentation, the fermentation is ended, and the obtained fermentation broth is extracted and separated to obtain the daptomycin.

Embodiment 2

[0022] A method for producing daptomycin by fed-batch decanal fermentation, comprising the following:

[0023] a. Cultivate Streptomyces roseospora seed solution: Transfer the preserved Streptomyces roseospora strain to the slant medium, cultivate at 30°C for 120h, then inoculate in liquid medium, and cultivate in a shaker at 30°C for 36h, that is Obtain the described Streptomyces roseospora seed solution.

[0024] b. Inoculation: inoculate the seed solution obtained in step a into the fermentation medium;

[0025] c. Fermentation culture: the inoculated medium obtained in step b is cultivated and fermented, and the fermentation temperature is 30-32°C;

[0026] d. Add cysteine: After 18 hours of fermentation, add decanal solution with a mass concentration of 6.0% (the solvent is a mixture of ethanol and water) to the fermentation broth, and the feeding speed is: per liter of fermentation broth Feed the fermenter at a flow rate of 1.0-2.0ml / h until the end of fermenta...

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Abstract

The invention provides a method for producing Daptomycin by fed-batch decyl aldehyde fermentation. A decyl aldehyde solution is supplemented into a fermentation tank in a Streptomyces roseosporus fermentation culture process to produce the Daptomycin. Thus, the method provided by the invention can enhance the yield of the Daptomycin. The method provided by the invention widens the path for producing Daptomycin by a fermentation process; and the decyl aldehyde solution has low toxicity for cells and can exist in the form of liquid at normal temperature, and thus, can not crystallize due to low temperature, thereby ensuring the fed-batch effect. Besides, the method is suitable for laboratory small-tank fermentation of Daptomycin, and also suitable for scale-up production in industrialized big tanks.

Description

[0001] technical field [0002] The invention belongs to the field of daptomycin production, and in particular relates to a method for producing daptomycin by fed-batch decanal fermentation. Background technique [0003] In the past 10 years, the trend of Gram-positive drug-resistant bacterial infections has been on the rise. At present, the difficulties in the clinical treatment of bacterial infections mainly focus on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and glycopeptide-sensitive Staphylococcus aureus (GISA). Pathogens with a high transmission rate and high fatality rate in hospitals, although vancomycin and other glycopeptide antibiotics have achieved certain curative effects in the treatment of such infections, but in recent years, vancomycin-resistant bacteria have been found clinically, and this The trend is gradually increasing. Therefore, research on new antibiotics against drug-resistant bacteria has become ...

Claims

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Application Information

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IPC IPC(8): C12P21/04C12R1/465
Inventor 朱辉韩晓彤
Owner CHENGDU YATU BIOLOGICAL TECH
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