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A kind of fermentation medium and culture method thereof for fermentative production of thiopeptide antibiotic nosiheptide

A technology of thiopeptide antibiotics and fermentation medium, which is applied in the direction of fermentation and peptides, can solve the problems of strains that have not reached the maximum production capacity, high production costs, unfavorable large-scale production, etc., and can improve the production level of bacteria , to avoid process instability, to avoid the effect of greening or decline

Active Publication Date: 2021-12-03
HEBEI SHENGXUE DACHENG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] 1. The C / N ratio of the basal medium is not suitable, resulting in a large change in the shape of the bacteria, and the ability to produce hormones is not high. Compared with foreign countries, the fermentation level of industrial production is generally low
[0006] 2. During the fermentation process, the nutrient requirements of different metabolic stages of the bacteria were not controlled differently, so that the ability of the strain to produce hormones was not maximized, which eventually led to high production costs and was not conducive to large-scale production

Method used

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  • A kind of fermentation medium and culture method thereof for fermentative production of thiopeptide antibiotic nosiheptide
  • A kind of fermentation medium and culture method thereof for fermentative production of thiopeptide antibiotic nosiheptide
  • A kind of fermentation medium and culture method thereof for fermentative production of thiopeptide antibiotic nosiheptide

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] seed culture

[0049] Seed medium (g / L): glucose 20, low-temperature soybean meal 20, corn steep liquor 10, ammonium sulfate 3.0, magnesium sulfate 0.5, calcium carbonate 5.0, potassium dihydrogen phosphate 0.2, soybean oil 3.0, defoamer 0.2;

[0050] The quality requirements of the sterilized seed medium are: amino nitrogen 80-120mg / 100mL, total sugar 3.0-5.0g / 100mL, pH 6.5-7.0.

[0051] Inoculate the cultured active Streptomyces strain bottle fermentation liquid into the seed medium according to the inoculation amount of 0.2-0.3%, and cultivate it. The tank pressure is 0.04±0.05Mp, the culture temperature is 30±1℃, the ventilation ratio is 0.8-1.0vvm, and the dissolved oxygen Control it at 30-50%. When the bacterial concentration reaches above 28% and the pH value drops to 6.6-7.0, the culture time is continued for 28-32 hours.

[0052] Wherein the quality requirement of cultured active Streptomyces strain bottle fermentation liquid is: bacteria concentration 30-40%...

Embodiment 2

[0064] seed culture

[0065] Seed medium (g / L): glucose 30, low-temperature soybean meal 25, corn steep liquor 15, ammonium sulfate 4.0, magnesium sulfate 0.8, calcium carbonate 8.0, potassium dihydrogen phosphate 0.5, soybean oil 5.0, defoamer 0.3;

[0066] The quality requirements of the sterilized seed medium are: amino nitrogen 80-120mg / 100mL, total sugar 3.0-5.0g / 100mL, pH 6.5-7.0.

[0067] Inoculate the cultured active Streptomyces strain bottle fermentation liquid into the seed medium according to the inoculation amount of 0.2-0.3%, and cultivate it. The tank pressure is 0.04±0.05Mp, the culture temperature is 30±1℃, the ventilation ratio is 0.8-1.0vvm, and the dissolved oxygen Control it at 30-50%. When the bacterial concentration reaches above 28% and the pH value drops to 6.6-7.0, the culture time is continued for 28-32 hours.

[0068] Wherein the quality requirement of cultured active Streptomyces strain bottle fermentation liquid is: bacteria concentration 30-40%...

Embodiment 3

[0080] seed culture

[0081] Seed medium (g / L): glucose 40, low-temperature soybean meal powder 30, corn steep liquor 20, ammonium sulfate 5.0, magnesium sulfate 1.0, calcium carbonate 10, potassium dihydrogen phosphate 0.8, soybean oil 8.0, defoamer 0.5;

[0082] The quality requirements of the sterilized seed medium are: amino nitrogen 80-120mg / 100mL, total sugar 3.0-5.0g / 100mL, pH 6.5-7.0.

[0083] Inoculate the cultured active Streptomyces strain bottle fermentation liquid into the seed medium according to the inoculation amount of 0.2-0.3%, and cultivate it. The tank pressure is 0.04±0.05Mp, the culture temperature is 30±1℃, the ventilation ratio is 0.8-1.0vvm, and the dissolved oxygen Control it at 30-50%. When the bacterial concentration reaches above 28% and the pH value drops to 6.6-7.0, the culture time is continued for 28-32 hours.

[0084] Wherein the quality requirement of cultured active Streptomyces strain bottle fermentation liquid is: bacteria concentration ...

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Abstract

The invention discloses a fermentation medium for fermenting and producing the thiopeptide antibiotic nosiheptide and a cultivation method thereof, and belongs to the technical field of microbial fermentation. The present invention has determined the optimal proportioning ratio of the seed culture medium and the fermentation medium nutrient substance of active Streptomyces fermenting to produce nosiheptide; the present invention controls the inorganic nitrogen level by variable speed adjustment of the acceleration rate of the ammonia water flow in the growth stage and the production stage of the bacterium. 5-10mg / 100mL and 15-25mg / 100mL realize the control of nitrogen source demand in different metabolic stages of bacteria, improve mycelium morphology, increase the level of bacteria production, reduce production costs, and obtain a stable, high-efficiency Process for producing nosiheptide by fermentation.

Description

technical field [0001] The invention belongs to the technical field of microbial fermentation, and relates to a fermentation medium for fermenting and producing a thiopeptide antibiotic nosiheptide and a cultivation method thereof. Background technique [0002] Nosiheptide, also known as Nosiceptide, is a thiopeptide antibiotic. There are 5 thiazole rings in the nosiheptide molecule, and the molecular formula is C 51 h 43 N 13 o 12 S 6 , the molecular weight is 1222.37. Nosiheptide is a light yellow or light brown powder with a melting point of 310-320°C and is insoluble in water. Nosiheptide has an obvious inhibitory effect on Gram-positive bacteria, and is known as an environmentally friendly feed additive because it can promote animal growth, improve feed utilization, and has no resistance, no residue, and is safe and pollution-free. [0003] In 1961, French scientists discovered nosiheptide in the fermented liquid, and it was approved to be listed as a feed additi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P21/02
CPCC07K5/06139C12P21/02
Inventor 李珊
Owner HEBEI SHENGXUE DACHENG PHARMA
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