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A kind of additive for improving epothilone fermentation yield and application thereof

A technology of epothilones and additives, which is applied in the field of fermentation and preparation of antineoplastic drugs, can solve the problems of low yield, numerous chemical total synthesis steps, and lack of cost advantages, and achieve good water solubility, promotion of absorption and utilization, and overall The effect of volume increase

Active Publication Date: 2018-11-13
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the many steps of chemical total synthesis, the yield is low, and it has no cost advantage compared with the biological fermentation method, so the biosynthesis method has become the mainstream direction of epothilone production and preparation technology research
However, the current improvement of epothilone fermentation technology is mainly focused on finding suitable carbon and nitrogen sources. After years of optimization of carbon and nitrogen sources, the method of improving epothilone production by optimizing the medium alone has reached a bottleneck period.
Therefore, it is necessary to explore other aspects or pathways to initiate or enhance the secondary metabolism of myxobacteria, but searching for patents or documents related to this aspect, especially the additives used to improve the fermentation yield of epothilone, has not been reported so far

Method used

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  • A kind of additive for improving epothilone fermentation yield and application thereof
  • A kind of additive for improving epothilone fermentation yield and application thereof
  • A kind of additive for improving epothilone fermentation yield and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] (1) Selection of fermentation strains: Sorangium Cellulosum So0157-2 among the myxobacteria strains.

[0039] (2) Activation of bacterial strains: the above-mentioned bacterial strains were inoculated on a solid plate medium, and the composition of the medium was: KNO 3 0.5g / L, Na 2 HPO 4 0.25g / L, MgSO4 ·7H 2 O 1g / L, FeCl 3 0.01g / L, trace element solution 1ml / L, agar 15g / L, pH 7.2. (After the plate is solidified, stick a 1.5×1.5cm square filter paper piece). Culture at 30°C for 7 days, inoculate into liquid medium, liquid The composition of the medium is: potato starch 8g / L, soybean peptone 2g / L, glucose 2g / L, yeast powder 2g / L, MgSO 4 1g / L, CaCl 2 1g / L, EDTA-Fe 3+ 1ml / L, trace element solution 1.0ml / L, pH 7.2.30°C, 200rpm for 5 days. Pour the above bacterial solution into a spinner bottle containing glass beads and disperse for 2 minutes, set aside.

[0040] (3) Fermentation culture: Take 3 mL of the above bacterial liquid and inoculate it into the epothilo...

Embodiment 2

[0054] (1) Selection of fermentation strains: Sorangium Cellulosum So0157-2 among the myxobacteria strains.

[0055] (2) Activation of bacterial strains: the above-mentioned bacterial strains were inoculated on a solid plate medium, and the composition of the medium was: KNO 3 0.5g / L, Na 2 HPO 4 0.25g / L, MgSO 4 ·7H 2 O 1g / L, FeCl 3 0.01g / L, trace element solution 1ml / L, agar 15g / L, pH 7.2. (After the plate is solidified, stick a 1.5×1.5cm square filter paper piece). Culture at 30°C for 7 days, inoculate into liquid medium, liquid The composition of the medium is: potato starch 8g / L, soybean peptone 2g / L, glucose 2g / L, yeast powder 2g / L, MgSO 4 1g / L, CaCl 2 1g / L, EDTA-Fe 3+ 1ml / L, trace element solution 1.0ml / L, pH 7.2.30°C, 200rpm for 5 days. Pour the above bacterial solution into a spinner bottle containing glass beads and disperse for 2 minutes, set aside.

[0056] (3) Fermentation culture: 3 mL of the above-mentioned bacterial liquid was inoculated into the epo...

Embodiment 3

[0070] (1) Selection of fermentation strains: Sorangium Cellulosum So0157-2 among the myxobacteria strains.

[0071] (2) Activation of bacterial strains: the above-mentioned bacterial strains were inoculated on a solid plate medium, and the composition of the medium was: KNO 3 0.5g / L, Na 2 HPO 4 0.25g / L, MgSO 4 ·7H 2 O 1g / L, FeCl 3 0.01g / L, trace element solution 1ml / L, agar 15g / L, pH 7.2. (After the plate is solidified, stick a 1.5×1.5cm square filter paper piece). Culture at 30°C for 7 days, inoculate into liquid medium, liquid The composition of the medium is: potato starch 8g / L, soybean peptone 2g / L, glucose 2g / L, yeast powder 2g / L, MgSO 4 1g / L, CaCl 2 1g / L, EDTA-Fe 3+ 1ml / L, trace element solution 1.0ml / L, pH 7.2.30°C, 200rpm for 5 days. Pour the above bacterial solution into a spinner bottle containing glass beads and disperse for 2 minutes, set aside.

[0072] (3) Fermentation culture: 3 mL of the above-mentioned bacterial liquid was inoculated into the epo...

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Abstract

The invention discloses an additive for increasing the fermentative yield of epothilone, which is indoleacetic acid, indole methyl formate or indole, and the added final concentration of the additive in epothilone liquid fermentation medium is 20 plus / minus 3Mu mol / L. An experiment proves that the additive disclosed by the invention can promote thalli to absorb and utilize nutrient substances and enhance the secondary metabolism of sprangium cellulosums, so that the total amount of epothilone is increased by 2 to 19 percent on average in comparison with the total amount of epothilone not added with the additive. The additive provided by the invention reduces fermentation cost, increases the yield of epothilone, and provides another approach for epothilone production.

Description

technical field [0001] The invention relates to an additive for fermentative production of epothilones and its application, in particular to an additive for increasing the fermentation yield of epothilones and its application, and belongs to the technical field of antitumor drug fermentation preparation. Background technique [0002] Epothilones are a class of antitumor drugs with great application prospects. Epothilones belong to polyketide macrolide compounds, which have a strong stabilizing effect on polymeric microtubules, and their mechanism of action is similar to paclitaxel. And it is more water-soluble than paclitaxel and has less cytotoxicity. This discovery has drawn extensive attention to epothilone, which involves its biochemical mechanism, chemical modification, activity and activity testing, clinical trials, production and biosynthesis, showing its great promise in the treatment of cancer. [0003] On October 16, 2007, the U.S. Food and Drug Administration (F...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/18C12R1/645
Inventor 李越中胡玮郑连帅古静燕
Owner SHANDONG UNIV
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