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A kind of method to promote the accumulation of staurosporine

A technology for staurosporine and vitamins, applied in the field of promoting staurosporine accumulation, can solve the problems of unfavorable large-scale industrial production, difficulty in realizing industrial production, high fermentation cost, etc., achieve large-scale industrial application, promote staurosporine The effect of bacterial accumulation and production cost reduction

Active Publication Date: 2021-10-29
ZHEJIANG HISUN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, patents CN108048369A and CN107603922A disclose methods for obtaining staurosporine by fermentation of staurosporine-producing Streptomyces, but the production strains all belong to the genus Marine Streptomyces, seawater needs to be added in the process, and macropores are also required in the process of patent CN107603922A Resin, the highest output is 320mg / L, the actual industrial application is poor
[0004] In order to overcome the shortcomings of the staurosporine fermentation technology, such as unstable strains, low yield, and difficulty in realizing industrial production, our company has bred a brand-new staurosporine-producing strain, which is disclosed in CN108676757A. This strain has the ability to produce It has the advantages of high capacity, high heritage stability, and obvious increase in fermentation yield. However, the disclosed fermentation method still has problems such as insufficient fermentation yield and high fermentation cost, which is not conducive to large-scale industrial production.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0026] The seed medium contains the following components per liter: 20g of glycerin, 20g of peanut powder, 7.5g of yeast powder, 10g of corn soluble starch, 8g of glucose, 2g of calcium carbonate, pH7.0. Sterilize at ℃ for 20min.

[0027] Seed solution culture method: Inoculate the grown fresh Streptomyces sp. HS-HY-153 strain into the seed medium, shaker speed 250r / min, culture at 28°C±1°C for 24h-32h, seed liquid The inoculation amount is 1-5% (volume percentage).

Embodiment 1

[0046] Insert the seed solution prepared in Preparation Example 1 into the fermentation medium (in 1 L) containing the following components: 50 g of glycerin, 20 g of peanut cake powder, 5 g of yeast powder, 3 g of calcium carbonate, 0.2 g of nicotinic acid, and 0.2 g of thiamine hydrochloride. g, the balance is water, pH 7.0, sterilized at 121°C for 20min, temperature at 26°C, shaken at 250r / min for 7d to obtain a fermentation broth. The fermentation liquid was detected by high-performance liquid chromatography, and the production of staurosporine was 1670ug / ml.

Embodiment 2

[0048] Insert the seed solution prepared in Preparation Example 1 into the fermentation medium (in 1 L) containing the following components: 50 g of glycerin, 20 g of peanut cake powder, 5 g of yeast powder, 3 g of calcium carbonate, 0.2 g of nicotinic acid, and 0.5 g of thiamine hydrochloride. g, the balance is water, pH 7.0, sterilized at 121°C for 20min, temperature at 26°C, shaken at 250r / min for 7d to obtain a fermentation broth. The fermentation liquid was detected by high-performance liquid chromatography, and the production of staurosporine was 1770ug / ml.

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Abstract

The invention provides a method for promoting the accumulation of staurosporine, and specifically discloses a culture medium for promoting the accumulation of staurosporine, which greatly promotes the accumulation of staurosporine by adopting different vitamin combinations and medium formulas. At the same time, by adding carbon source, the fermentation yield can be increased by more than 40%. The technical scheme provided by the invention is simple and feasible, further improves the production efficiency of the staurosporine, reduces production costs, and facilitates the industrial production and application of the staurosporine.

Description

technical field [0001] The invention relates to the technical field of industrial microbial fermentation, in particular to a method for promoting staurosporine accumulation. Background technique [0002] Staurosporine is an indole alkaloid isolated from Streptomyces staurosporeus in 1977. It has various biological activities such as antibacterial, antifungal, lowering blood pressure, inhibiting platelet aggregation and protecting nerves, especially staurosporine It is also a broad-spectrum kinase inhibitor and has the potential to be developed into an antitumor drug. However, scientists later discovered that its kinase inhibitory activity has poor specificity (it can interact with 90% of the human kinases discovered so far), and the resulting toxic side effects limit the possibility of its becoming a drug. For this reason, pharmacists have synthesized a large number of derivatives, hoping to improve the kinase-specific inhibition of these compounds. Among them, midostaurin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/18C12N1/20C12N1/38C12R1/465
CPCC12N1/20C12N1/38C12P17/188
Inventor 项仁鑫方佳双杨小虎邓爱文姜南应灵萍尹继龙王冠徐晓艳
Owner ZHEJIANG HISUN PHARMA CO LTD
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