Method for producing norvancomycin by fermentation

A technology of norvancomycin and fermentation broth, which is applied in the direction of fermentation, peptides, bacteria, etc., can solve the problems of feedback inhibition, low fermentation level, and reduce feedback inhibition of bacteria, so as to improve production capacity and equipment utilization, and reduce feedback The effect of suppressing and reducing emissions

Inactive Publication Date: 2016-04-20
NCPC NEW DRUG RES & DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] 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 absorb norvancomycin in the fermentation broth, reduce the feedback inhibition to the producing bacteria, promote the biosynthesis of norvancomycin, and increase the production of norvancomycin

Method used

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  • Method for producing norvancomycin by fermentation
  • Method for producing norvancomycin by fermentation
  • Method for producing norvancomycin by fermentation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1、500

[0030] Embodiment 1, 500mL shake flask fermentation prepares norvancomycin

[0031] Preparation of Seed Solution of Amycolatopsis Hebei Strain

[0032] Inoculate the slant culture or spore liquid of Amycolatopsis hebei strain into the seed medium, and culture at 26°C, 220 rpm, for 72 hours to obtain the seed liquid;

[0033] The seed culture medium described therein is obtained 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.

[0034] The strain preservation number of the norvancomycin-producing bacteria of the present invention is CCTCC203099.

[0035] Fermentation medium composition:

[0036] Glucose 20.0g, corn flour 40.0g, hot-pressed soybean cake powder 20.0g, corn steep liquo...

Embodiment 2、5

[0040] Embodiment 2, 5L automatic fermenter fermentation prepares norvancomycin

[0041] Preparation of Seed Solution of Amycolatopsis Hebei Strain

[0042]Inoculate the slant culture or spore liquid of Amycolatopsis hebei strain into the seed medium, and culture at 28°C, 220rpm, for 64h to obtain the seed liquid;

[0043] 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.

[0044] The strain preservation number of the norvancomycin-producing bacteria of the present invention is CCTCC203099.

[0045] Fermentation medium composition:

[0046] 90.0 grams of glucose, 90.0 grams of corn flour, 45.0 grams of hot-pressed soybean cake powd...

Embodiment 3、10

[0050] Embodiment 3, 10L automatic fermenter fermentation prepares norvancomycin

[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 cultivate 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:

[0056] Glucose 150.0 grams, corn flour 100.0 grams, cottonseed protein powder 5...

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Abstract

The invention belongs to the field of fermentation engineering and particularly relates to a method for producing norvancomycin by fermentation. In this method, by adding super-paramagnetic microspheres in a norvancomycin synthesis phase to adsorb norvancomycin in a fermentation broth, a reduction is given to the feedback inhibition of a fermentation product upon generated bacteria and an improvement is given to the biological synthesis of norvancomycin. After fermentation, fermentation unit of the norvancomycin is up to 22593 ug / ml; compared with a method adding no super-paramagnetic microspheres, this method provides an increase of greater than 35% in norvancomycin yield, an improvement in productivity and equipment utilization and a reduction in wastewater and waste residue discharge.

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): C12P21/02
CPCC07K9/008C12N1/20C12P21/02
Inventor 张雪霞任风芝王耀耀赵颖李晓露耿文飞郑智慧段宝玲路新华高任龙
Owner NCPC NEW DRUG RES & DEV
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