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Fermentation promoter for improving output of gentamycin C1a, and adding method thereof

A fermentation accelerator, the technology of gentamicin, applied in the field of fermentation engineering, can solve the problems of not being able to change the balance point of the enzyme reaction in the organism, increasing the risk of converting to primary metabolism, and having no clear and complete explanation, so as to facilitate fermentation Effects of production, change of rheological properties, increase of permeability

Active Publication Date: 2017-04-26
HENAN RENHUA BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the invention patent (CN95102511) "a method for producing gentamicin", it is disclosed that an appropriate amount of precursor substances are added to the medium to shorten the fermentation cycle and increase the yield. Regarding the precursor substances, three types are mainly disclosed Amino acids (methionine, lysine and arginine), although the methyl group in methionine can be incorporated into the gentamicin molecule, but it cannot change the balance point of the enzyme reaction in the organism, and the result is not obvious for the increase in potency
Some precursors will be transferred to primary metabolism, which is obviously unfavorable for the synthesis of gentamicin by secondary metabolism
Experiments have shown that when methionine is added in excess, biosynthesis turns to basal metabolism, lecithin is synthesized, and even cytokinin is synthesized, resulting in a sharp drop in the production of antibiotics
[0004] Since gentamicin C1a medium has used organic nitrogen sources to form various amino acids after proteolysis, the effect of simply adding amino acid precursors is not obvious enough, but it will increase the risk of switching from secondary metabolism to primary metabolism
[0005] For a long time, how to effectively improve the production of gentamicin C1a has always been a difficult problem in the production of gentamicin. People have also done a lot of research, trying to explain theoretically the interaction between the components in the fermentation process of gentamicin. Transformation mechanism and how to effectively control the content of C1a, but due to the complex factors affecting the components during the fermentation process, even if the large process remains unchanged, any small process fluctuations will have a certain impact on the components
Therefore, so far, there is no clear and complete explanation

Method used

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  • Fermentation promoter for improving output of gentamycin C1a, and adding method thereof
  • Fermentation promoter for improving output of gentamycin C1a, and adding method thereof

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preparation example Construction

[0016] The preparation method of described fermentation accelerator: at first be to join the D-xylose of corresponding quality, N-acetylglucosamine, ammonium ferrous sulfate, betaine and 2-deoxystreptamine into deionized water, then place 45 ℃, 150rpm magnetic heating stirrer until it is completely dissolved, and then filtered through a microporous filter with a pore size of 0.22 µm to obtain a sterile fermentation accelerator for future use.

[0017] Warm the prepared fermentation accelerator in a water bath at 30-36°C for 15-30 minutes, then add it to the fermentation medium at a ratio of 0.001-0.005% of the volume of the fermentation medium to directly participate in the fermentation process; or mix the prepared According to the ratio of 0.001-0.005% of the feed volume, the fermentation accelerator is added to the feed, and is added to the fermentation medium to participate in fermentation along with the feed; or the above two methods are used in combination, and the ferment...

Embodiment 1

[0019] The fermentative production method of embodiment 1 gentamicin Cla

[0020] The production of gentamicin C1a usually adopts the form of graded fermentation. The gentamicin C1a producing bacterium Micromonospora is prepared by spores and mycelia cultured in shake flasks, and then put into the seed tank. Connect to the fermenter for cultivation, during the cultivation process, feed materials according to the specific situation, the specific operation of the fermentation process is as follows:

[0021] 1. Configuration of culture medium

[0022] Incline medium: K 2 HPO 4 0.01%, NaCl 0.05%, MgSO 4 0.05%, glucose 0.1%, corn flour 2% and agar powder 2%, the rest is water, and the percentages are mass percentages;

[0023] Mycelium medium: K 2 HPO 4 0.01%, NaCl 0.05%, MgSO 4 0.05%, glucose 1% and corn flour 2%, the rest is water, and the percentages are mass percentages;

[0024] First-level seed culture medium: the feeding configuration is carried out according to ...

Embodiment 2

[0042] Add the fermentation accelerator whose volume percentage is 0.002% in the feeding material, but do not add it in the fermentation medium. Other specific fermentation process techniques (medium configuration, spore culture, primary seed cultivation, secondary seed cultivation, fermentation cultivation and feeding control) are the same as in Example 1.

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Abstract

The invention relates to a fermentation promoter for improving the output of gentamycin C1a, and an adding method thereof, and belongs to the technical field of fermentation engineering. The fermentation promoter comprises, by mass, 20-50% of D-xylose, 10-30% of N-acetylglucosamine, 1-5% of ammonium ferrous sulfate, 5-10% of betaine, 0.01-0.05% of 2-deoxystreptamine, and the balance of deionized water. 0.001-0.005% Of the fermentation promoter is added to a fermentation medium or an additional medium, and then participates in the fermentation process in a single or combined form. The fermentation promoter optimizes the fermentation environment, promotes metabolism of thalluses, is simply and effectively added, enhances the thallus fermentation performance, and improves the output by 46%.

Description

technical field [0001] The invention belongs to the technical field of fermentation engineering, specifically relates to the fermentation production of gentamicin, in particular to a fermentation accelerator and an adding method for increasing the yield of gentamicin C1a. Background technique [0002] Gentamicin C1a, as one of the main components of gentamicin, is an important aminoglycoside antibiotic and the mother nucleus of a semi-synthetic new drug ictimicin, which is the first in China and has independent intellectual property rights. The traditional method of preparing C1a is to use resin separation technology to extract C1a single component from multi-component gentamycin. Due to the similar structure and similar physical and chemical properties of each component, the extraction cost remains high, and the high cost in the market The price of purity C1a remains high. Therefore, it is of great significance to study the fermentation of gentamicin C1a. [0003] During ...

Claims

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Application Information

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IPC IPC(8): C12P19/48C12R1/29
CPCC12P19/485
Inventor 程国政
Owner HENAN RENHUA BIOTECH CO LTD
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