Method for producing pingyangmycin by fermentation

A technology of pingyangmycin and fermentation products, applied in the field of fermentation engineering, can solve the problems of unstable fermentation production level, large workload and little effect, and achieve the effects of improving industrial fermentation level, production level and output.

Active Publication Date: 2020-01-17
JILIN AODONG PHARMACEUTICAL INDUSTRY GROUP YANJI CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, domestic research methods to improve Pingyangmycin mainly focus on strain selection, optimization of fermentation medium prescriptions, and changes in fermentation process. Although certain achievements have been made, the workload is huge and the results are minimal. The level of fermentation in industrialized production refers to Pingyangmycin alone. The target product of the component is generally 50-80U / ml and the fermentation production level is extremely unstable

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  • Method for producing pingyangmycin by fermentation
  • Method for producing pingyangmycin by fermentation
  • Method for producing pingyangmycin by fermentation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1: Shake flask pingyangmycin fermentation precursor comparison

[0039] The culture of the strain is activated, the cell is expanded, and finally the seed solution of Streptomyces verticillium (product of Beina Industrial Microbial Library, code BNCC215870) is transferred to the fermentation medium for fermentation to produce pingyangmycin. This example is divided into For the control group, the test group 1, the test group 2, the test group 3, the test group 4, and the test group 5, three repetitions are set for each group, that is, the control group is D-1, D-2 and D-3, and the test group 1 is Sl-1, S-1-2 and S-1-3, test group 2 is S-1-L-1, S-1-L-2 and S-1-L-3, test group 3 is S- 2-1, S-2-2 and S-2-3, test group 4 is S-2-L-1, S-2-L-2 and S-2-L-3, test group 5 is S- 3-1, S-3-2 and S-3-3, the final test results are averaged.

[0040] 1. Preparation of precursor solution and fermentation medium:

[0041] Configuration A1: 2.4mg / ml adenosylmethionine solution; A2: 4.8...

Embodiment 2

[0049] Example 2 Determination of the addition ratio of exogenous precursors and the fermentation unit (titer) of the target product of pingyangmycin produced by the fermentation of Streptomyces verticillium by carbon source and nitrogen source

[0050] 1. The orthogonal experiment was used to test the interaction of the ratio of exogenous precursors and the carbon source and nitrogen source in the fermentation. Among them, the concentration of adenosylmethionine in the fermentation medium, spermidine The concentration in the fermentation medium, the mass percentage of maltose in the fermentation medium, and the mass percentage of soy peptone in the fermentation medium are respectively set at three levels, as shown in Table 2.

[0051] Among them, the fermentation medium is prepared: the fermentation medium is configured according to the ratio of maltose and soy peptone in the fermentation medium as described in Table 2, and the mass percentages of other components are starch 3.0%, ...

Embodiment 3

[0060] Example 3 Shaking flask to produce pingyangmycin

[0061] Activate the culture, expand the culture, and finally inoculate the seed solution of Streptomyces verticillium (product of Beina Industrial Microbiology Bank, code BNCC215870) into the fermentation medium for fermentation to produce Pingyangmycin, the control group and the test group Set up three repetitions, that is, the control group is CG-1, CG-2 and CG-3, and the test group is EG-1, EG-2 and EG-3. The final test results are averaged. The specific test steps are as follows:

[0062] 1. Preparation of exogenous precursor solution and fermentation medium:

[0063] Configure a composite solution of 2.4mg / ml adenosylmethionine solution + 9.6mg / ml spermidine solution: take 0.24g of adenosylmethionine and 0.96g of spermidine, dissolve it with sterile purified water, Dilute the purified water to 100ml of water to obtain a composite solution. The prepared composite solution is sterilized and filtered with a sterile filter m...

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Abstract

The invention discloses a method for producing pingyangmycin by fermentation. The method for producing pingyangmycin by fermentation comprises the steps that streptoverticillium is fermented in a fermentation medium, an exogenous precursor is added into the fermentation medium during the fermentation to obtain pingyangmycin-containing fermentation product, and the pingyangmycin is isolated and obtained from the fermentation product; the exogenous precursor is a substance A and / or a substance B, the substance A is adenosylmethionine or a similar amino acid derivative of the adenosylmethionine,and the substance B is spermidine or a spermidine salt. The method for producing the pingyangmycin by fermentation is simple, effective, the level of pingyangmycin fermentation production can be quickly increased, the production cost is lowered, additional devices and manpower are not required, the level of pingyangmycin industrial fermentation can be greatly increased, and the method is suitablefor industrial scale production.

Description

Technical field [0001] The invention belongs to the field of fermentation engineering, and specifically relates to a method for fermentation and production of pingyangmycin. Background technique [0002] Pingyangmycin is a single-component glycopeptide antibiotic with anti-tumor activity found from the fermentation product of Streptomyces verticillium. The terminal amine is spermidine. Pingyangmycin is a broad-spectrum, low-toxicity anti-tumor drug. It has a good effect on malignant lymphoma, head and neck cancer and breast cancer. It also has a relatively satisfactory effect on liver cancer without effective drug treatment. Therefore, it is of great significance to increase the content of pingyangmycin in the fermentation broth, increase production output, and meet market demand. [0003] At present, the domestic research methods to improve Pingyangmycin mainly focus on the selection of strains and the optimization of fermentation medium prescriptions to change the fermentation...

Claims

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Application Information

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IPC IPC(8): C12P21/02C12N1/20C12R1/465
CPCC07K9/003C12N1/20C12P21/005
Inventor 袁天阳陈庆源张海涛朱颖禹学军
Owner JILIN AODONG PHARMACEUTICAL INDUSTRY GROUP YANJI CO LTD
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