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Method for producing tetracycline by fermentation of streptomyces aureus

A technology based on Streptomyces aureus and tetracycline, applied in the direction of microorganism-based methods, biochemical equipment and methods, fermentation, etc., can solve the problems of abnormal red-turning metabolism of fermentation broth, poor stirring and ventilation effects, and dyspnea of ​​bacteria, etc., to achieve Effects of controlling metabolic rate, shortening holding time, and saving sterilization steam

Active Publication Date: 2014-02-26
NINGXIA QIYUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the prior art, in the fermentation process of producing tetracycline by fermentation of Streptomyces aureus, a large amount of late-acting carbon and nitrogen sources such as soybean cake powder and starch are used, and there is a phenomenon of incomplete utilization, and nearly 50% of the nutrients are still available after the fermentation is over. The substance has not been fully utilized, which not only causes waste of raw materials, but also causes difficulties in subsequent extraction due to a large amount of residual carbon and nitrogen sources when the fermentation broth is put into the tank
Moreover, in the fermentation process, the process of passing ammonia is usually adopted. This kind of concentrated formula medium (the concentration of various raw materials in the fermentation medium is relatively large, and the medium formula suitable for the process of passing ammonia is usually called concentrated formula. ) and the process of passing ammonia, it is difficult to control the early stage of fermentation, mycelium often grows too fast, and the fermentation liquid becomes very viscous, resulting in poor stirring and ventilation effects, insufficient oxygen supply, difficulty in breathing the bacteria, and finally the fermentation liquid turns Abnormal red metabolism, decreased production level

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] 1. The preparation of the spore slope and the preparation of the seeds are the same as those of the comparative example.

[0046] 2. Fermentation medium:

[0047] Medium ratio: starch 30g / L, dextrin: 5g / L, soybean flour: 6g / L, corn steep liquor 15-30g / L, ammonium sulfate 2-6g / L, light calcium carbonate 3.5-5g / L, Sodium bromide 0.5-1.5g / L, potassium dihydrogen phosphate 0.05-0.1g / L, amylase 0.1g / L. It is prepared according to the weight-to-volume ratio of the medium, and the temperature of damp heat sterilization is 118°C, and it is incubated for 20 minutes.

[0048]Insert the seed culture solution into the sterilized medium according to the inoculum amount of 10-20%, culture at 29-33°C, ventilation at 1:0.6v / v / min, stir, dissolve oxygen above 20% during fermentation, and cultivate 160-180 hr put into the tank to obtain a fermented liquid containing tetracycline.

[0049] 3. Mixture preparation:

[0050] Mixing ratio: starch 300g / L, 20% hydrolyzed soybean meal: 40g / L...

Embodiment 2

[0057] 1. The preparation of the spore slope and the preparation of the seeds are the same as those of the comparative example.

[0058] 2. Fermentation medium:

[0059] Medium ratio: starch 35g / L, dextrin: 7.5g / L, soybean powder: 8g / L, corn steep liquor 15-30g / L, ammonium sulfate 2-6g / L, light calcium carbonate 3.5-5g / L , sodium bromide 0.5-1.5g / L; potassium dihydrogen phosphate: 0.05-0.1g / L, amylase 0.1g / L. It is prepared according to the weight-to-volume ratio of the medium, and the temperature of damp heat sterilization is 119°C, and it is incubated for 20 minutes.

[0060] Put the seed culture solution into the sterilized medium according to the inoculum amount of 10-20%, culture at 29-33°C, ventilation at 1:0.8v / v / min, stir, and dissolve oxygen above 20% during the fermentation process. 160-180 hr put into the tank to obtain a fermented liquid containing tetracycline.

[0061] 3. Mixture preparation:

[0062] Mixing ratio: starch 350g / L, 20% hydrolyzed soybean meal: ...

Embodiment 3

[0069] 1. The preparation of the spore slope and the preparation of the seeds are the same as those of the comparative example.

[0070] 2. Fermentation medium:

[0071] Medium ratio: starch 40g / L, dextrin: 10g / L, soybean flour: 10g / L, corn steep liquor 15-30g / L, ammonium sulfate 2-6g / L, light calcium carbonate 3.5-5g / L, Sodium bromide 0.5~1.5g / L, potassium dihydrogen phosphate 0.05~0.1g / L, amylase 0.1g / L. It is prepared according to the weight-to-volume ratio of the medium, and the temperature of damp heat sterilization is 120°C, and it is incubated for 20 minutes.

[0072] Insert the seed culture solution into the sterilized medium according to the inoculum amount of 10-20%, culture at 29-33°C, ventilation at 1:1.0v / v / min, stir, dissolve oxygen above 20% during the fermentation process, and cultivate 160-180 hr put into the tank to obtain a fermented liquid containing tetracycline.

[0073] 3. Mixture preparation:

[0074] Mixing ratio: starch 400g / L, 20% hydrolyzed soyb...

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PUM

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Abstract

The invention relates to a method for producing tetracycline by fermentation of streptomyces aureus. The method comprises the following steps: slant spore culture, seed culture and fermentation culture of the streptomyces aureus, and is characterized in that dextrin, sucrose, corn pulp, hydrolyzed soybean meal and other medium-effect carbon-nitrogen sources are adopted to replace original late-effect carbon-nitrogen sources; by reducing the contents of starch and bean flour in an original fermentation culture medium and combining with a formula of a mixture in the fermentation process and adjustment of a replenishing method and placing part of the nitrogen sources in the fermentation culture medium into material replenishment in the fermentation process, the concentration of the culture medium in the fermentation process is effectively controlled, the oxygen dissolution condition in the early stage of fermentation is improved, the final residue of the culture medium of fermentation is controlled by material replenishment, the material consumption is reduced, and the emission of solid wastes is reduced; the metabolism velocity in exponential growth phase in the fermentation process of the tetracycline is effectively controlled, the abnormal situations that a fermentation solution turns red and becomes sour and the like in the fermentation process are reduced, and the fermentation level is improved.

Description

technical field [0001] The invention relates to the technical field of biological fermentation, in particular to a method for fermenting and producing tetracycline by Streptomyces aureus. Background technique [0002] Tetracycline is an antibacterial substance produced by fermentation with Streptomyces aureus as the fermentation strain, and it has good inhibitory effects on Gram-positive bacteria, negative bacteria, rickettsia, viral viruses, spirochetes and even protozoa It is a broad-spectrum antibiotic. [0003] In the prior art, in the fermentation process of producing tetracycline by fermentation of Streptomyces aureus, a large amount of late-acting carbon and nitrogen sources such as soybean cake powder and starch are used, and there is a phenomenon of incomplete utilization, and nearly 50% of the nutrients are still available after the fermentation is over. The substance is not fully utilized, which not only causes waste of raw materials, but also causes difficulties...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P29/00C12R1/49
Inventor 孙瑞君郭海燕张志
Owner NINGXIA QIYUAN PHARMA
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