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Fermentation process for raising ebomycin A yield

A technology of epothilone and fermentation process, which is applied in the direction of fermentation, etc., and can solve the problems of unreported literature or patents, high cost, and reduced feedback inhibition

Inactive Publication Date: 2002-09-04
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The deficiency of the above-mentioned fermentation technology method is: 1) due to the agglomeration properties of myxobacteria growing in liquid, the improvement of the number of thalline cells is affected, thereby limiting the production of myxobacteria metabolite epothilones; 2) producing epothilones The fermentation conditions of bleomycin are too complicated and the cost is high, and potato starch, glucose, defatted soybean protein and yeast extract are not the most suitable carbon and nitrogen sources for bleomycin production; 3) to reduce the metabolism of myxobacteria Feedback inhibition of epothilone on the product, the XAD-16 resin added during the fermentation process is expensive, and this resin can only adsorb low-polarity metabolites, for other medium-polar or high-polarity metabolites Feedback inhibition has no effect, etc.
[0005] In view of the above-mentioned deficiencies, the literature or patents for improving related technologies and methods have not been reported so far.

Method used

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  • Fermentation process for raising ebomycin A yield
  • Fermentation process for raising ebomycin A yield
  • Fermentation process for raising ebomycin A yield

Examples

Experimental program
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Effect test

Embodiment 1

[0037] Example 1: (1) Fermentation strain Sorangium cellulosum (Sorangium cellulosum) ATCC15384 among myxobacteria strains was selected. (2) Under the premise of maintaining the synthesis ability of metabolites, the myxobacteria strains are domesticated by liquid culture and uniform growth: the above-mentioned strains are inoculated on a solid slant medium, and the solid medium components are: soybean peptone 8g / L, potato starch 20g / L , CaCl 2 .2H 2 O 1g / L, MgSO 4 .7H 2 O 1g / L, Fe-EDTA 8mg / L, agar powder 15g / L; 30°C, after cultivating for 5 days, inoculate into liquid fermentation medium, the composition of liquid fermentation medium is: soybean peptone 10g / L, potato starch 20g / L , CaCl 2 .2H 2 O 1g / L, MgSO 4 .7H 2 O 1g / L, Fe-EDTA 8mg / L; 30°C, 120 rpm shaker culture for 7 days, the above-mentioned culture bacteria were reconnected to the solid medium for culture, and then cultured according to the original conditions and then inoculated into the liquid fermentation medi...

Embodiment 2

[0038] Example 2: (1) Sorangium cellulosum (Sorangium cellulosum) ATCC15384 among the myxobacteria strains was selected for fermentation. (2) Under the premise of maintaining the synthesis ability of metabolites, the myxobacteria strains are domesticated by liquid culture and uniform growth: the above-mentioned strains are inoculated on a solid slant medium, and the solid medium components are: soybean peptone 10g / L, potato starch 22g / L , CaCl 2 .2H 2 O 1g / L, MgSO 4 .7H 2 O 1g / L, Fe-EDTA 8mg / L, agar powder 15g / L; 30°C, after cultivating for 5 days, inoculate into liquid fermentation medium, the composition of liquid fermentation medium is: soybean peptone 12g / L, potato starch 23g / L , CaCl 2 .2H 2 O 1g / L, MgSO 4 .7H 2 O 1g / L, Fe-EDTA 8mg / L; 30°C, 120 rpm shaker culture for 5 days, the above-mentioned culture bacteria were reconnected to the solid medium for culture, and then cultured according to the original conditions and then inoculated into the liquid fermentation me...

Embodiment 3

[0039] Example 3: (1) Fermentation strain Sorangium cellulosum (Sorangium cellulosum) ATCC15384 among myxobacteria strains was selected. (2) Under the premise of maintaining the synthesis ability of metabolites, the myxobacteria strains are acclimated to uniform growth in liquid culture: inoculate the above-mentioned strains on a solid slant medium, and the components of the solid medium are: soybean peptone 6g / L, potato starch 17g / L , CaCl 2 .2H 2 O 1g / L, MgSO 4 .7H 2 O 1g / L, Fe-EDTA 8mg / L, agar powder 15g / L; 30°C, after cultivating for 5 days, inoculate into liquid fermentation medium, the composition of liquid fermentation medium is: soybean peptone 7g / L, potato starch 17g / L , CaCl 2 .2H 2 O 1g / L, MgSO 4 .7H 2O 1g / L, Fe-EDTA 8mg / L; 30°C, 120 rpm shaker culture for 7 days, the above-mentioned culture bacteria were reconnected to the solid medium for culture, and then cultured according to the original conditions and then inoculated into the liquid fermentation medium ...

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Abstract

The present invention discloses a method for raising secondary metallic product output of myxobacteria, i,e, a method for raising output of metabolic product epothilone A of sorangium cellulosum of ephothilone in myxobacteria, and the said method incldues: 1). naturalization method of lump-grown myxobacterial liquid uniform growth; (2). selecting potato starch and hydrolyzed lactoprotein, etc. suitable for production of epothilone A; and 3). addition method of mixed resin for integrally-eliminating product metabolic accumulation so as to make the output of ephothiloue A product be up to 62.7 mg / L level.

Description

(1) Technical field [0001] The invention relates to a method for increasing the yield of metabolites of myxobacteria, in particular to a method for increasing the yield of epothilone A of S. cellulosum in myxobacteria. (2) Background technology [0002] At present, the most successful clinical anti-tumor chemotherapy drug is paclitaxel, a natural compound that promotes microtubule polymerization.  ) and its analog docetaxel (Taxotere  ), has been used in the treatment of solid cancers such as ovarian cancer, thymus cancer, colon cancer, lung cancer and liver cancer. The success of the inducible anti-tumor drug paclitaxel and its shortcomings in chemotherapy (low water solubility and cell drug resistance during chemotherapy, etc.) prompted researchers to further screen for drugs with better chemical, biological and pharmacological properties. microtubule stabilizer. However, after a long time and a lot of screening, it was not until recent years that four new natural com...

Claims

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Application Information

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IPC IPC(8): C12P17/02
Inventor 李越中胡玮刘新利韩冠君
Owner SHANDONG UNIV
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