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Method for improving erythromycin fermentation titer and promoting erythromycin A synthesis

A kind of erythromycin, potency technology

Active Publication Date: 2012-10-31
宁夏泰瑞制药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Domestic erythromycin fermentation level is generally not high, 2000-5000 u / ml lower than the international advanced level, poor competitiveness

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1 Improve the technology of erythromycin fermentation yield and erythromycin A content

[0039] Streptomyces rubrum was used as the strain for producing erythromycin.

[0040] use 2m 3 Cultivate primary seeds in a fermenter: culture temperature 32°C, aeration ratio 0.5-0.9 m 3 / (m 3 min), tank pressure 0.03~0.06MPa, stirring speed 200r / min, primary seed medium (kg / m 3 ) formula is: corn flour 40, ammonium sulfate 1.5, sodium chloride 0.6, peptone 2.5, yeast powder 4.0, glucose 5.0, calcium carbonate 1.0, magnesium sulfate 0.5, dipotassium hydrogen phosphate 0.5, corn steep liquor 3.0, edible oil 5.0, Bacterial pre-adjustment pH7.0.

[0041] Pour all the first-level seeds into 15m 3 In the fermenter, further expand the cultivation of seeds, the cultivation temperature is 32°C, and the aeration ratio is 0.5-0.9 m 3 / (m 3 min), tank pressure 0.03~0.06MPa, stirring speed 200r / min, secondary seed medium (kg / m 3 ) formula is: corn flour 25, diammonium h...

Embodiment 2

[0045] Embodiment 2 Improve the technology of erythromycin fermentation yield and erythromycin A content

[0046] Streptomyces rubrum was used as the strain for producing erythromycin.

[0047] use 2m 3 Cultivate primary seeds in a fermenter: culture temperature 32°C, aeration ratio 0.5-0.9 m 3 / (m 3 min), tank pressure 0.03~0.06MPa, stirring speed 200r / min, primary seed medium (kg / m 3 ) formula is corn flour 40, ammonium sulfate 1.5, sodium chloride 0.6, peptone 2.5, yeast powder 4.0, glucose 5.0, calcium carbonate 1.0, magnesium sulfate 0.5, dipotassium hydrogen phosphate 0.5, corn steep liquor 3.0, edible oil 5.0, sterilization Top adjust pH7.0.

[0048] Pour all the first-level seeds into 15m 3 In the fermenter, further expand the cultivation of seeds, the cultivation temperature is 32°C, and the aeration ratio is 0.5-0.9 m 3 / (m 3 min), tank pressure 0.03~0.06MPa, stirring speed 200r / min, secondary seed medium (kg / m 3 ) formula is corn flour 25, diammonium hydroge...

Embodiment 3

[0051] Embodiment 3 Improve the technology of erythromycin fermentation yield and erythromycin A content

[0052] Streptomyces rubrum was used as the strain for producing erythromycin.

[0053] use 2m 3 Cultivate primary seeds in a fermenter: culture temperature 32°C, aeration ratio 0.5-0.9 m 3 / ( m 3 min), tank pressure 0.03~0.06MPa, stirring speed 200r / min, primary seed medium (kg / m 3 ) formula is corn flour 40, ammonium sulfate 1.5, sodium chloride 0.6, peptone 2.5, yeast powder 4.0, glucose 5.0, calcium carbonate 1.0, magnesium sulfate 0.5, dipotassium hydrogen phosphate 0.5, corn steep liquor 3.0, edible oil 5.0, sterilization Top adjust pH7.0.

[0054] Pour all the first-level seeds into 15m 3 In the fermenter, further expand the cultivation of seeds, the cultivation temperature is 32°C, and the aeration ratio is 0.5-0.9 m 3 / ( m 3 min), tank pressure 0.03~0.06MPa, stirring speed 200r / min, secondary seed medium (kg / m 3 ) formula is corn flour 25, diammonium hydro...

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Abstract

The invention relates to a method for improving erythromycin fermentation titer and promoting erythromycin A synthesis. The method comprises the steps of: during the fermentation tank fermentation culture process of producing erythromycin utilizing streptomyces erythreus as seeds through fermentation, adopting an erythromycin fermentation basic formula which contains betaine, edible oil and trace elements, controlling the corresponding biomass concentration, ventilation ratio, fermentation tank pressure, fermentation temperature, stirring rate and pH and the edible oil concentration in a fermentation liquor to produce erythromycin through fermentation, and adding a Tween-20 surfactant during the fermentation process. According to the invention, through creating an environment which is contributed to the antibiotics production of streptomyces erythreus, the streptomyces erythreus metabolism is developed towards the direction which is benefit to erythromycin synthesis, finally, the erythromycin fermentation cost is lowered, and the erythromycin fermentation titer and the erythromycin A synthesis are improved.

Description

technical field [0001] The invention belongs to the technical field of biomedical fermentation, and in particular relates to a method for increasing the fermentation titer of erythromycin and promoting the production of erythromycin A. Background technique [0002] Erythromycin is a class of fourteen-membered macrolide antibiotics, including erythromycin A (EMA), erythromycin B (EMB), erythromycin C (EMC), erythromycin D (EMD ), erythromycin E (EME) and erythromycin F (EMF). Erythromycin A is widely used clinically. It has the highest antibacterial activity, its antibacterial spectrum is similar to that of penicillin, and it has strong antibacterial activity against Gram-positive bacteria, such as hemolytic streptococcus, pneumococcus, Streptococcus viridans and Bacillus diphtheriae also have antibacterial effects on Gram-negative bacteria such as meningococcus, Neisseria gonorrhoeae, Influenza bacilli, Bacillus pertussis, Brucella and Legionella, and are commonly used clin...

Claims

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Application Information

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IPC IPC(8): C12P19/62C12R1/465
Inventor 王义任勇杜以文奇乃纳卓斌
Owner 宁夏泰瑞制药股份有限公司