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Culture medium for fermentation production of erythromycin with red streptomyces and fermentation method thereof

A fermentation medium and a technology of Streptomyces rubrum, applied in the field of biomedicine, can solve the problems of affecting oxygen supply, waste of raw materials, and increasing the viscosity of fermentation liquid, so as to reduce the energy consumption of oxygen supply and ventilation, reduce the cost of raw materials, and reduce the utilization of oil Effect

Active Publication Date: 2018-02-02
NINGXIA QIYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of late-acting organic nitrogen sources such as soybean cake powder increases the viscosity of the fermentation broth, affects the oxygen supply, and there is a phenomenon of incomplete utilization in the late stage of fermentation, and the addition of late-acting carbon sources such as oils and fats also has insufficient utilization. Complete phenomenon, and cause the oxygen consumption of bacteria to increase, so the use of slow-acting carbon and nitrogen sources not only causes waste of raw materials, but also causes difficulties in subsequent extraction due to a large amount of residual carbon sources when the fermentation broth is put into tanks
[0004] To sum up, the use of a large amount of late-acting organic nitrogen sources such as soybean cake powder has resulted in low fermentation levels of erythromycin, and it is difficult to improve the fermentation level. There is little room for fermentation process changes and difficult process breakthroughs
Moreover, in the erythromycin fermentation feed, natural vegetable oils such as soybean oil, rapeseed oil, and cottonseed oil are usually used as the main carbon source material used by the bacteria in the fermentation process. Vegetable oils are not completely decomposed in the process of being decomposed by the bacteria. Phenomenon, the utilization rate is slow, the decomposition and utilization lag, resulting in more residual oil in the fermentation broth, which affects the filtration speed and product quality of the fermentation broth, the fermentation unit is low, and the consumption of raw materials is increased, and the fermentation cost is high

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] 1. Seed cultivation:

[0028] Seed culture medium composition: starch 1.2%, corn steep liquor 2.0%, ammonium sulfate 0.15%, light calcium carbonate 0.35%, zinc sulfate 0.01%, magnesium sulfate 0.1%, appropriate amount of antifoaming agent, the rest is water, in weight percentage. Sterilize for later use.

[0029] The slant spores were inoculated into a sterilized seed culture medium and cultivated at a culture temperature of 33° C., aeration rate of 1:0.7 v / v / min, stirring, and cultivation for 41 hours to obtain a seed liquid.

[0030] 2. Fermentation culture:

[0031] Inoculate the seed liquid obtained in process 1 into a sterilized fermentation medium at 25% of the inoculum. The culture temperature is 32~34℃, aerate, stir, control the dissolved oxygen in the fermentation process to more than 30%, and monitor the amino nitrogen during the culture. And total sugar: when the amino nitrogen content in the fermentation broth drops below 30%, ammonia is passed, and the amino nitro...

Embodiment 2

[0036] 1. Seed cultivation:

[0037] Seed culture medium composition: starch 2.0%, corn steep liquor 3.0%, ammonium sulfate 0.35%, light calcium carbonate 0.62%, zinc sulfate 0.02%, magnesium sulfate 0.2%, appropriate amount of antifoaming agent, the rest is water, in weight percentage. Sterilize for later use.

[0038] The slant spores were inoculated and cultured in a sterilized first-level seed culture medium at a culture temperature of 34°C, aeration rate of 1:0.8v / v / min, stirring, and cultured for 45 hours to obtain a seed solution.

[0039] 2. Fermentation culture:

[0040] Inoculate the seed liquid obtained in process 1 into a sterilized fermentation medium at a 20% inoculum amount and cultivate at a culture temperature of 34-35°C, aerate and stir, control the dissolved oxygen in the fermentation process to more than 30%, and monitor the amino nitrogen during the culture process And total sugar: when the amino nitrogen in the fermentation broth drops below 30%, ammonia is pass...

Embodiment 3

[0045] 1. Seed cultivation:

[0046] Seed culture medium composition: starch 3%, corn steep liquor 4%, ammonium sulfate 0.55%, light calcium carbonate 0.8%, zinc sulfate 0.03%, magnesium sulfate 0.3%, appropriate amount of antifoaming agent, the rest is water, in weight percentage. Sterilize for later use.

[0047] The slant spores were inoculated into a sterilized first-level seed medium and cultivated at a culture temperature of 35° C., aeration rate of 1:1.0 v / v / min, stirring, and culture for 50 hours to obtain a seed solution.

[0048] 2. Fermentation culture:

[0049] Inoculate the seed liquid obtained in process 1 into a sterilized fermentation medium at a 15% inoculum amount for cultivation. The cultivation temperature is 34~35℃, aeration and stirring are used to control the dissolved oxygen in the fermentation process to more than 30%, and the amino nitrogen is monitored during the cultivation process. And total sugar: when the amino nitrogen content in the fermentation broth...

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Abstract

The invention relates to culture medium for fermentation production of erythromycin with red streptomyces and a fermentation method thereof. The culture medium includes seed culture medium and fermentation culture medium, wherein the seed culture medium is prepared from starch, corn steep liquor, ammonium sulfate, light calcium carbonate, zinc sulfate, magnesium sulfate and a right amount of defoaming agent, and the fermentation culture medium is prepared from starch, corn steep liquor, ammonium sulfate, calcium carbonate, magnesium sulfate, zinc sulfate and a right amount of defoaming agent.According to the culture medium and the fermentation method, through change of the formula structures of the seed culture medium and the fermentation culture medium, change of the formula structure and control means of additional medium and introduction of several trace elements, the metabolic pathway of cells is changed, so that tertiary fermentation is shortened to secondary fermentation, and the fermentation time is shortened; meanwhile, the cost of fermentation raw materials is reduced, the fermentation culture medium is diluted, oxygen supply in the fermentation process is improved, and energy consumption of oxygen supply is reduced; through implementation of the technology, the fermentation level of erythromycin is significantly improved, and erythromycin E in the product is significantly reduced.

Description

Technical field [0001] The invention belongs to the technical field of biomedicine, and particularly relates to a culture medium for producing erythromycin by fermentation of Streptomyces rubrum and a fermentation method thereof. Background technique [0002] Erythromycin (Er) is a class of macrolide antibiotics, mainly including erythromycin A (ErA), erythromycin B (ErB), erythromycin C (ErC) and erythromycin E (ErE) ) And other components, among which erythromycin A has the strongest antibacterial activity, while B, C and E have lower antibacterial activity. Erythromycin fermentation uses a kind of actinomycete as the production strain, which is prepared into slant spores after rejuvenation, separation, and spore culture. Then the slant spores are connected to the seed tank for seed expansion and cultivation, and finally connected to the fermentation medium. The process of controlling the culture temperature, pH, substrate concentration, etc. to control the primary and seconda...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/62C12N1/20C12R1/465
CPCC12N1/20C12P19/62
Inventor 郭海燕孙瑞君郭惠芬胡晓玲
Owner NINGXIA QIYUAN PHARMA
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