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A process for producing lincomycin by fed-batch fermentation

A technology of lincomycin and fed-batch fermentation, applied in the field of microbial fermentation, can solve the problems of indeterminate lincomycin content, unfavorable lincomycin fermentation production, and inability to control the cultivation process, etc., and achieve low B component content , the effect of stable environment and stable environment

Active Publication Date: 2019-01-11
JIANGXI GUOYAO PHARMA LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The fermentation process of Streptomyces lincomycin is only regulated by regulating the concentration of ammonium ions. Although the output of lincomycin has increased, the content of lincomycin B in the product cannot be determined, and the output of lincomycin is still to be determined. improve
In the prior art, many adopt the method of fed-batch feeding, which not only cannot accurately control the cultivation process, but also has high local reducing sugar and amino nitrogen content in the feed liquid before and after feeding, which may affect the growth of bacteria. Metabolism produces inhibition, resulting in large differences in the growth of bacteria in the fermenter, which is extremely unfavorable to the fermentation production of lincomycin

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] The invention relates to a process for producing lincomycin by fed-batch fermentation. The process flow includes: seed culture, shake flask culture, secondary tank culture and fermenter fermentation culture.

[0054] Seed medium (g / L): soybean cake powder 25, soluble starch 8, glucose 20, corn steep liquor 20, ammonium sulfate 0.8, magnesium sulfate 0.6, potassium dihydrogen phosphate 0.4, sterilized at 121°C for 30 minutes.

[0055] Shake flask medium (g / L): soybean cake powder 30, soluble starch 10, glucose 20, molasses 15, corn steep liquor 25, ammonium nitrate 1.0, calcium carbonate 0.5, magnesium sulfate 0.5, dipotassium hydrogen phosphate 0.3, extinguished at 121°C Bacteria 30min.

[0056] Secondary tank culture medium (g / L): soybean cake powder 35, soluble starch 15, glucose 40, corn steep liquor 30, biotin 0.5, ammonium nitrate 0.5, ammonium sulfate 0.5, calcium carbonate 1.5, potassium dihydrogen phosphate 0.5, chloride Sodium chloride 1.5, foam enemy 3.0mL / L,...

Embodiment 2

[0066] The invention relates to a process for producing lincomycin by fed-batch fermentation. The process flow includes: seed culture, shake flask culture, secondary tank culture and fermenter fermentation culture.

[0067] Seed medium (g / L): soybean cake powder 25, soluble starch 8, glucose 20, corn steep liquor 20, ammonium sulfate 0.8, magnesium sulfate 0.6, potassium dihydrogen phosphate 0.4, sterilized at 121°C for 30 minutes.

[0068] Shake flask medium (g / L): soybean cake powder 35, soluble starch 12, glucose 25, molasses 20, corn steep liquor 30, ammonium nitrate 1.2, calcium carbonate 0.7, magnesium sulfate 0.6, dipotassium hydrogen phosphate 0.5, extinguished at 121°C Bacteria 30min.

[0069] Secondary tank culture medium (g / L): soybean cake powder 35, soluble starch 15, glucose 40, corn steep liquor 30, biotin 0.7, ammonium nitrate 0.5, ammonium sulfate 0.5, calcium carbonate 1.5, potassium dihydrogen phosphate 0.5, chloride Sodium chloride 1.5, foam enemy 3.0mL / L,...

Embodiment 3

[0079] The invention relates to a process for producing lincomycin by fed-batch fermentation. The process flow includes: seed culture, shake flask culture, secondary tank culture and fermenter fermentation culture.

[0080]Seed medium (g / L): soybean cake powder 25, soluble starch 8, glucose 20, corn steep liquor 20, ammonium sulfate 0.8, magnesium sulfate 0.6, potassium dihydrogen phosphate 0.4, sterilized at 121°C for 30 minutes.

[0081] Shake flask medium (g / L): soybean cake powder 40, soluble starch 15, glucose 30, molasses 25, corn steep liquor 35, ammonium nitrate 1.5, calcium carbonate 0.8, magnesium sulfate 0.8, dipotassium hydrogen phosphate 0.6, extinguished at 121°C Bacteria 30min.

[0082] Secondary tank culture medium (g / L): soybean cake powder 35, soluble starch 15, glucose 40, corn steep liquor 30, biotin 0.8, ammonium nitrate 0.5, ammonium sulfate 0.5, calcium carbonate 1.5, potassium dihydrogen phosphate 0.5, chloride Sodium chloride 1.5, foam enemy 3.0mL / L, ...

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Abstract

The invention relates to a process for producing lincomycin by fed-batch fermentation, which comprises seed culture, shake flask culture, secondary tank culture and fermentation culture in a fermentor. During the fermentation process, a small material is added which contains 8-12 parts of soybean cake powder, 15-20 parts of corn syrup, 4-5 parts of calcium carbonate, 2-3 parts of magnesium sulfate, 0.2-0.4 parts of leucine, and dimethyl silicone oil. 3-0.5 parts, soybean oil 0.3-0.5 parts and water 200 parts; ammonium sulfate solution or ammonia water is added as needed to regulate the pH of fermentation broth; the sugar solution is regulated as needed to keep the reducing sugar content in the fermentation broth in an appropriate range. The titer of lincomycin obtained by fermentation withthe process provided by the invention is more than 10000U / mL, and the content of B component in the separated and purified lincomycin is less than 0.5%.

Description

technical field [0001] The invention belongs to the technical field of microbial fermentation, and in particular relates to a process for producing lincomycin by fed-batch fermentation. Background technique [0002] Lincomycin belongs to the lincosamide class of antibiotics and is a narrow-spectrum antibiotic that acts on the 50S subunit of the ribosome of sensitive bacteria to prevent the extension of the peptide chain, thereby inhibiting the protein synthesis of bacterial cells, and has a good effect on Gram-positive cocci , especially for anaerobic bacteria, Staphylococcus aureus and pneumococcus have high antibacterial effect. Its mechanism of action is similar to that of erythromycin, and it is a bacteriostatic agent. It is mainly used clinically for various infections caused by sensitive bacteria, such as pneumonia, meningitis, endocarditis, cellulitis, tonsillitis, erysipelas, furuncle and urinary system infection etc. Because this product can enter bone tissue and ...

Claims

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Application Information

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IPC IPC(8): C12P17/16
CPCC12P17/16
Inventor 钟益清万义斌葛友群左飞鸿杨明何琳余凯丁永绥
Owner JIANGXI GUOYAO PHARMA LLC
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