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Fed-batch method for improving fermentation yield of teicoplanin

A technology of teicoplanin and feeding material is applied in the field of feeding feeding for improving the fermentation yield of teicoplanin, which can solve the problem of high cost and achieve the effects of low cost, improving fermentation yield and promoting energy material metabolism.

Active Publication Date: 2020-06-19
LIVZON GROUP FUZHOU FUXING PHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the existing technology is the Chinese invention patent with the application number 201410729473.5, by adding the feed medium to the fermentation medium during the fermentation process, the factors that inhibit the secondary metabolic pathway of teicoplanin can be reduced, and the teicoplanin can be improved. The yield of laning fermentation, but this method is costly, and it is prone to the problem of feedback inhibition effect caused by foaming and escaping of feed liquid in the later stage of fermentation, adding glucose and other carbon sources

Method used

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  • Fed-batch method for improving fermentation yield of teicoplanin

Examples

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Effect test

Embodiment 1

[0020] A feeding method for improving the fermentation yield of teicoplanin, specifically comprising the following steps:

[0021] 1) Seed culture: inoculate Actinoplanes teichomyceticus into the seed medium, and cultivate in a 30L test tank with a culture period of 50±16h to obtain seed liquid;

[0022] Seed medium formula (in parts by mass): 2.0 parts of soybean cake powder, 0.5 parts of yeast powder, 0.5 parts of peptone, 2.5 parts of glucose, 2 parts of starch, 0.4 parts of sodium chloride, 0.02 parts of potassium dihydrogen phosphate, 0.3 parts of calcium carbonate share;

[0023] Culture conditions: temperature 28°C, ventilation volume v:v=1:1.5, tank pressure 0.05Mpa, rotation speed 300rpm, initial pH value 7.2;

[0024] 2) Fermentation culture: Inoculate the cultivated seed liquid into the fermentation medium according to the inoculation amount of 6%, and cultivate it in a 50L test tank, and the culture period is 90-102h;

[0025] Fermentation medium formula (in part...

Embodiment 2

[0033] The difference between embodiment 2 and embodiment 1 is:

[0034] When the fermentation culture reaches 20-30 hours, start to feed 15% sodium acetate solution, and the flow rate is 0.29mL / (h·L);

[0035] When the fermentation culture reaches 30-50h, the flow acceleration rate changes to 0.23mL / (h·L);

[0036] When the fermentation culture reaches 50-90h, the flow acceleration rate changes to 0.17mL;

[0037] The average tank batch yield of Example 2 was 4.89 g / L.

Embodiment 3

[0039] The difference between embodiment 3 and embodiment 1 is:

[0040] When the fermentation culture reaches 30-40 hours, start to feed 15% sodium acetate solution, and the flow rate is 0.29mL / (h·L);

[0041] When the fermentation culture reaches 40-60h, the flow acceleration rate changes to 0.23mL / (h·L);

[0042] When the fermentation culture reaches 60-102h, the flow acceleration rate changes to 0.17mL.

[0043] The average tank batch yield of Example 3 was 4.83 g / L.

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Abstract

The invention discloses a fed-batch method for improving the fermentation yield of teicoplanin, and belongs to the technical field of biological fermentation. The fermentation mode of the teicoplaninis fed-batch fermentation, the feeding mode is fed-batch feeding, the fed-batch substance is a sodium acetate solution, the fed-batch feeding time is from the first logarithmic phase of fed-batch fermentation to the end of the fermentation, and the feeding speed is gradually reduced in the fed-batch feeding process. According to the fed-batch method provided by the invention, the feeding speed iscontrolled for feeding the sodium acetate solution from the first logarithmic phase to the fermentation termination phase of teicoplanin fermentation, so that the fermentation yield of the teicoplaninis remarkably increased and can reach 4.8 g / L. Meanwhile, compared with a fed-batch carbon source, the fed-batch sodium acetate solution does not cause a feedback inhibition effect, and the problemsof insufficient fermentation unit sequent and bubbling and liquid escaping of feed liquid in the later fermentation period are also avoided; and the fed-batch method is low in cost, simple in process,easy to popularize and easy to use in large-scale production.

Description

technical field [0001] The invention belongs to the technical field of biological fermentation, and in particular relates to a feeding method for improving the fermentation yield of teicoplanin. Background technique [0002] Teicoplanin, also known as pepticomycin, is a new glycopeptide antibiotic produced by Actinoplanes teichomyceticus through biological fermentation. It is another treatment for severe Gram's after vancomycin. Positive bacterial infection is the most effective weapon against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). [0003] The relative molecular mass of teicoplanin is about 1900, which consists of 7 molecules of amino acids and 3 molecules of sugar groups and acyl fatty acid side chains. The main active ingredient is TA2, which is composed of 5 compounds with very similar chemical structures (TA2-1, TA2-2, TA2-3, TA2-4 and TA2-5), and the difference of the 5 components is only in the ...

Claims

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Application Information

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IPC IPC(8): C07K9/00C12P21/02C12N1/20C12R1/045
CPCC12P21/005C07K9/008C12N1/20
Inventor 周兵兵暨火兴傅贞博巫秋萍
Owner LIVZON GROUP FUZHOU FUXING PHARMACEUTICAL CO LTD
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