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Fermentation process for preparing cephalosporin C and fermentation medium used in fermentation process

A technology of fermentation medium and fermentation method, applied in the field of biopharmaceuticals, to achieve broad industrial application prospects, improve fermentation titer, and promote the effect of biosynthesis ability

Active Publication Date: 2015-01-07
SHANXI WEIQIDA PHARMA IND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The effect of L-α-aminoadipic acid on ACV synthase and the final CPC (cephalosporin C) synthesis has not been reported

Method used

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  • Fermentation process for preparing cephalosporin C and fermentation medium used in fermentation process
  • Fermentation process for preparing cephalosporin C and fermentation medium used in fermentation process
  • Fermentation process for preparing cephalosporin C and fermentation medium used in fermentation process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Fermentation medium

[0055] The composition is as follows: D-α-aminoadipic acid 7g / L; peanut powder 35g / L; cottonseed protein 22g / L; gluten powder 45g / L; bean cake powder 24g / L; corn steep liquor 48mL / L; glucose 7g / L ; sucrose 12g / L; methionine 11g / L; ammonium sulfate 13g / L; calcium sulfate 14g / L; calcium carbonate 7g / L; soybean oil 105mL / L; and PPG20001mL / L.

[0056] Preparation: Mix and dissolve gluten powder and soybean oil, and dissolve other raw materials with deionized water as a solvent. After dissolving, mix and settle in a fermenter. Use 20% (w / v) sodium hydroxide solution to adjust the initial pH of the medium to 7.2 ~7.4 (during fermentation, as the fermentation proceeds, the pH of the fermentation broth gradually drops to 5.2~5.8).

[0057] Fermentation for the preparation of cephalosporin C

[0058] step 1:

[0059] Get Cephalosporium acremonium and carry out slant culture activation, and slant culture medium is composed of: take deionized water as ...

Embodiment 2

[0075] Fermentation medium

[0076] The composition is as follows: L-α-aminoadipic acid 12g / L; peanut powder 45g / L; cottonseed protein 30g / L; gluten powder 50g / L; bean cake powder 35g / L; corn steep liquor 70mL / L; glucose 10g / L ; sucrose 20g / L; methionine 15g / L; ammonium sulfate 20g / L; calcium sulfate 18g / L; calcium carbonate 9g / L; soybean oil 120mL / L; and PPG20002mL / L.

[0077] Preparation: Mix and dissolve gluten powder and soybean oil, and dissolve other raw materials with deionized water as a solvent. After dissolving, mix and settle in a fermenter. Use 20% (w / v) sodium hydroxide solution to adjust the initial pH of the medium to 7.2 ~7.4.

[0078] Fermentation for the preparation of cephalosporin C

[0079] step 1:

[0080] Get Cephalosporium acremonium and carry out slant culture activation, and slant medium is composed of: take deionized water as medium, wort juice 12g / L, peptone 10g / L, and agar 22g / L, pH before eliminating is 7.2; Slant culture method is: Cultiv...

Embodiment 3

[0096] Fermentation medium

[0097] The composition is as follows: D-α-aminoadipic acid 10g / L; peanut powder 40g / L; cottonseed protein 25g / L; gluten powder 45g / L; bean cake powder 32g / L; corn steep liquor 65mL / L; glucose 9g / L ; sucrose 19g / L; methionine 14g / L; ammonium sulfate 19g / L; calcium sulfate 17g / L; calcium carbonate 8g / L; soybean oil 115mL / L;

[0098] Preparation: Mix and dissolve gluten powder and soybean oil, and dissolve other raw materials with deionized water as a solvent. After dissolving, mix and settle in a fermenter. Use 20% (w / v) sodium hydroxide solution to adjust the initial pH of the medium to 7.2 ~7.4.

[0099] Fermentation for the preparation of cephalosporin C

[0100] step 1:

[0101] Get Cephalosporium acremonium and carry out slant culture activation, and slant culture medium is composed of: take deionized water as medium, wort juice 10g / L, peptone 10g / L, and agar 22g / L, pH before eliminating is 7.4; Slant culture method is: Cultivate for 11 ...

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Abstract

The invention relates to a fermentation process for preparing cephalosporin C and a fermentation medium used in the fermentation process. The fermentation process for preparing the cephalosporin C comprises the following steps: firstly, taking cephalosporium acremonium, activating, inoculating the activated cephalosporium acremonium to a seed culture medium, and culturing for 60-80 hours at the pH value of 6.8-7.2 at the temperature of 27-30 DEG C for preparing seeds; secondly, inoculating the seeds obtained in the step one to the fermentation medium, and fermenting for 110-150 hours at the pH value of 5.2-5.8 at the temperature of 24-29 DEG C; thirdly, carrying out centrifugal separation on fermentation liquor obtained in the step two, and taking supernatant liquid at the upper layer, so as to obtain cephalosporin C supernatant liquor. The fermentation process for preparing the cephalosporin C has the advantages that aminoadipic acid is added into the fermentation medium, a nutrient composition formula of the fermentation medium and fermentation technological conditions are optimized, biosynthesis capacity of the cephalosporin C is enhanced, fermentation titer is obviously increased, titer of the cephalosporin C is 38061-44837 microgram / mL, and quality of the cephalosporin C is not influenced, so that the fermentation process for preparing the cephalosporin C has a broad industrial application prospect.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and relates to a fermentation method for preparing cephalosporin C and a fermentation medium used in the fermentation method. Background technique [0002] Cephalosporin C is a metabolite of Cephalosporium acremonium and is another important β-lactam antibiotic after penicillin. Its structural formula is as follows: [0003] [0004] Cephalosporin C is a semi-synthetic precursor of cephalosporin antibiotics, and its production level determines the market supply of cephalosporin antibiotics. The in-depth study and process optimization of the fermentation method for the preparation of cephalosporin C has important social and economic significance. For example, optimizing the fermentation process can increase the fermentation titer, thereby improving production efficiency and reducing production costs. [0005] Factors affecting the fermentation level of the preparation of cephalospo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P35/06C12R1/75
CPCC12P35/06
Inventor 苗瑞春彭亮亮冯涛李树有任广宏张虎
Owner SHANXI WEIQIDA PHARMA IND
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