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Method for producing norvancomycin through fermentation

A technology of norvancomycin and fermentation broth, applied in the field of fermentation engineering, can solve the problems of feedback inhibition, low fermentation level, and reduce the feedback inhibition of producing bacteria, so as to improve production capacity and equipment utilization rate, reduce feedback inhibition, and promote production Effect

Active Publication Date: 2017-06-06
NCPC NEW DRUG RES & DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to solve the problem of feedback inhibition and low fermentation level of the high-concentration product that exists in the preparation of norvancomycin by microbial fermentation in the prior art, and to provide a method that optimizes the fermentation medium formula and fermentation conditions, and Adding superparamagnetic microspheres during the fermentation process to adsorb norvancomycin in the fermentation broth, reducing the feedback inhibition to the producing bacteria, promoting the biosynthesis of norvancomycin, and increasing the production of norvancomycin

Method used

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  • Method for producing norvancomycin through fermentation
  • Method for producing norvancomycin through fermentation
  • Method for producing norvancomycin through fermentation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1, 500mL shake flask fermentation preparation of norvancomycin (soybean cake powder, superparamagnetic microspheres)

[0033] Preparation of Seed Solution of Amycolatopsis Hebei Strain

[0034] Inoculate the slant culture or spore liquid of Amycolatopsis hebei strain into the seed medium, and cultivate at 26°C, 220 rpm, for 72 hours to obtain the seed liquid;

[0035] The seed culture medium described therein is prepared by the following method: 0.2 grams of cornstarch, 4.0 grams of glucose, 0.2 grams of hot-pressed soybean cake powder, 1.0 grams of yeast powder, 0.8 grams of corn steep liquor, 0.05 grams of sodium chloride, magnesium sulfate heptahydrate 0.05 g, 0.3 g calcium carbonate, add tap water to make up to 100 mL, pH 6.5, sterilize at 121°C for 30 min.

[0036] The strain preservation number of the norvancomycin-producing bacteria of the present invention is CCTCC203099.

[0037] Fermentation medium composition:

[0038]Glucose 20.0g, corn flour 40.0...

Embodiment 2、5

[0041] Example 2, Preparation of norvancomycin by fermentation in a 5L automatic fermenter (cottonseed protein powder and soybean cake powder, superparamagnetic microspheres)

[0042] Preparation of Seed Solution of Amycolatopsis Hebei Strain

[0043] Inoculate the slant culture or spore liquid of Amycolatopsis hebei strain into the seed medium, and cultivate at 28°C, 220 rpm, for 64 h to obtain the seed liquid;

[0044] The seed culture medium described therein is prepared by the following method: 3.0 grams of cornstarch, 20.0 grams of glucose, 10.0 grams of hot-pressed soybean cake powder, 5.0 grams of yeast powder, 5.0 grams of corn steep liquor, 1.0 grams of sodium chloride, magnesium sulfate heptahydrate 1.0 grams, 4.0 grams of calcium carbonate, add tap water to 1000mL, pH6.8, sterilize at 121°C for 30min.

[0045] The strain preservation number of the norvancomycin-producing bacteria of the present invention is CCTCC203099.

[0046] Fermentation medium composition:

...

Embodiment 3、10

[0050] Example 3, Preparation of norvancomycin by fermentation in 10L automatic fermenter (cottonseed protein powder and yeast powder, superparamagnetic microspheres)

[0051] Preparation of Seed Solution of Amycolatopsis Hebei Strain

[0052] Inoculate the slant culture or spore liquid of Amycolatopsis hebei strain into the seed medium, and culture at 30°C, 220 rpm, for 48 hours to obtain the seed liquid;

[0053] The seed culture medium described therein is obtained by the following method: 4.0 grams of cornstarch, 10.0 grams of glucose, 8.0 grams of hot-pressed soybean cake powder, 8.0 grams of yeast powder, 2.0 grams of corn steep liquor, 2.0 grams of sodium chloride, magnesium sulfate heptahydrate 2.0 grams, 6.0 grams of calcium carbonate, add tap water to make up to 1000mL, pH7.0, sterilize at 121°C for 30min.

[0054] The strain preservation number of the norvancomycin-producing bacteria of the present invention is CCTCC203099.

[0055] Fermentation medium composition...

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Abstract

The invention belongs to the technical field of fermentation engineering, and particularly relates to a method for producing norvancomycin through fermentation. The method is achieved through the following measures: 1) optimizing the formula of a fermentation culture medium; 2) adding superparamagnetic microspheres during fermentation synthesis of the norvancomycin to reduce feedback inhibition of a fermentation product on producing bacteria and promote biosynthesis of the norvancomycin. After fermentation, the fermentation titer unit of the norvancomycin can reach 22593 micrograms per milliliter; compared with the process in which the superparamagnetic microspheres are not added, the method provided by the invention has the advantages as follows: the yield of the norvancomycin is increased by more than 35%, the productivity and the equipment utilization rate are improved, and the discharge of waste water and waste residues is reduced.

Description

technical field [0001] The invention belongs to the field of fermentation engineering, in particular to a method for producing norvancomycin by fermentation. Background technique [0002] Norvancomycin hydrochloride is the only glycopeptide antibiotic independently developed and successfully used clinically in my country. It is produced by Streptomyces fermentation and used to treat Gram-positive bacterial infections. Norvancomycin has similar chemical structure, pharmacological properties, antibacterial activity and antibacterial spectrum to vancomycin. Its mechanism of action is to inhibit the synthesis of bacterial cell walls. Drug of choice for severe infections. [0003] The norvancomycin molecule is composed of two basic structures, the glycosyl part α-o-vancosamine-β-o-glucosyl and the central heptapeptide core of the peptidyl part, and norvancomycin salt is used clinically acid salt, the molecular formula is C 65 h 73 Cl 2 N 9 o 24 • HCl, molecular weight 1471...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P21/02C12N1/20C12R1/01
CPCC07K9/008C12N1/20C12P21/02
Inventor 张雪霞任风芝李晓露王耀耀赵颖耿文飞王海燕李丽红李宁高月麒郑智慧段宝玲路新华高任龙
Owner NCPC NEW DRUG RES & DEV
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