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A method for fermenting and producing Pingyangmycin

A technology of Pingyangmycin and fermentation products, which is applied in the field of fermentation engineering, can solve the problems of little effect, unstable fermentation production level, heavy workload, etc., and achieve the effects of increasing production, improving industrial fermentation level, and improving production level

Active Publication Date: 2021-09-21
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

Method used

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  • A method for fermenting and producing Pingyangmycin
  • A method for fermenting and producing Pingyangmycin
  • A method for fermenting and producing Pingyangmycin

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Experimental program
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Effect test

Embodiment 1

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

[0039] Strain activation culture, thalline expansion culture, finally the seed solution of Streptomyces verticillium (the product of Bei Na Industrial Microorganism Bank, code is BNCC215870) is transplanted to fermentation medium and fermented and produced Pingyangmycin, the present embodiment divides For the control group, test group 1, test group 2, test group 3, test group 4 and 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 S-l-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: 4.8mg / ml adenosyl...

Embodiment 2

[0049] Embodiment 2 Determination of the addition ratio of exogenous precursors and carbon source and nitrogen source to ferment Streptomyces verticillium to produce the fermentation unit (titer) of Pingyangmycin target product

[0050] 1. Orthogonal experiments were used to test the interaction of factors such as the addition ratio of exogenous precursors and carbon sources and nitrogen sources in fermentation. Among them, the concentration of adenosylmethionine in the fermentation medium, the concentration of spermidine The concentration in the fermentation medium, the mass percentage of maltose in the fermentation medium and the mass percentage of soybean peptone in the fermentation medium were respectively set at three levels, see Table 2 for details.

[0051] Wherein, the preparation of fermentation medium: configure the fermentation medium according to the ratio of maltose and soybean peptone in the fermentation medium described in Table 2, and the mass percentages of oth...

Embodiment 3

[0060] Embodiment 3 shaking flask produces Pingyangmycin

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

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

[0063] Prepare a compound solution of 2.4 mg / ml adenosylmethionine solution + 9.6 mg / ml spermidine solution: take 0.24 g of adenosylmethionine and 0.96 g of spermidine, dissolve them in sterilized purified water, and Bacteria-purified water was distilled to 100ml water enough to obtain a composite solution, and the prepared composite solution...

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Abstract

The invention discloses a method for producing pingyangmycin by fermentation. The invention discloses a method for fermenting and producing Pingyangmycin, which comprises fermenting Streptomyces verticillium in a fermentation medium, and adding exogenous precursors to the fermentation medium during the fermentation process to obtain the fermentation medium containing Pingyangmycin The product is isolated from the fermentation product to obtain Pingyangmycin; wherein, the exogenous precursor is substance A and / or substance B, and the substance A is adenosylmethionine or its similar amino acid derivatives, The substance B is spermidine or a salt of spermidine. The fermentative production method of Pingyangmycin provided by the present invention is simple and effective, can rapidly improve the fermentation production level of Pingyangmycin, reduce production cost, does not need additional equipment and manpower, can greatly improve the industrial fermentation level of Pingyangmycin, and is suitable for industrial scale production.

Description

technical field [0001] The invention belongs to the field of fermentation engineering, and in particular relates to a method for producing pingyangmycin by fermentation. Background technique [0002] Pingyangmycin is a single-component glycopeptide antibiotic with antitumor activity discovered from the fermentation product of Streptomyces verticillium, and the terminal amine is spermidine. Pingyangmycin is a broad-spectrum, low-toxic antineoplastic drug. It has good curative effect on malignant lymphoma, head and neck cancer and breast cancer. It also has a satisfactory curative effect on liver cancer that has no effective drug treatment. Therefore, it is of great significance to improve the content of Pingyangmycin in the fermented liquid, increase the production output, and meet the market demand. [0003] At present, domestic research methods to improve Pingyangmycin mainly focus on strain selection, optimization of fermentation medium prescriptions, and changes in fer...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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