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A kind of fermentation promoter and adding method for improving the output of gentamicin c1a

A fermentation accelerator, gentamicin technology, applied in the field of fermentation engineering, can solve the problems of inability to change the balance point of enzyme reactions in organisms, increase the risk of converting to primary metabolism, and complex factors of components, so as to facilitate fermentation production , changing the rheological properties, the effect of fermentation index and yield improvement

Active Publication Date: 2020-12-15
HENAN RENHUA BIOTECH CO LTD
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  • 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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  • A kind of fermentation promoter and adding method for improving the output of gentamicin c1a
  • A kind of fermentation promoter and adding method for improving the output of gentamicin c1a

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preparation example Construction

[0016]The preparation method of the fermentation promoter: first add the corresponding quality of D-xylose, N-acetylglucosamine, ferrous ammonium sulfate, betaine and 2-deoxystreptamine to deionized water, and then place it in 45 ℃, 150rpm magnetic heating stirrer up to complete dissolution, and then filtered through a microporous filter with a pore size of 0.22μm, to prepare a sterile fermentation promoter, ready for use.

[0017]Warm the prepared fermentation promoter in a 30-36°C water bath for 15-30 minutes, and 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 Fermentation enhancer of the feed is added to the feed in the proportion of 0.001-0.005% of the feed volume, and added to the fermentation medium with the feed to participate in the fermentation; or the above two methods are used in combination in the fermentation medium and the feed Fermentation promoters are add...

Embodiment 1

[0019]Example 1 Fermentation production method of gentamicin Cla

[0020]The production of gentamicin C1a usually adopts the form of graded fermentation. The micromonospora gentamicin C1a-producing bacteria is prepared by spores, cultured with shake flask hyphae, and then connected to the seed tank. Connected to the fermenter for cultivation, and feeding according to the specific conditions during the cultivation process, the specific operation of the fermentation process is as follows:

[0021]1. The configuration of the culture medium

[0022]Slant medium: K2HPO4 0.01%, NaCl 0.05%, MgSO4 0.05%, glucose 0.1%, corn flour 2% and agar powder 2%, the rest is water, where the percentage is the mass percentage;

[0023]Mycelium medium: K2HPO4 0.01%, NaCl 0.05%, MgSO4 0.05%, glucose 1%, corn meal 2%, the rest is water, and the percentage is the mass percentage;

[0024]Primary seed culture medium: feed and configure according to the composition ratio in Table 1, the remaining components are water, and t...

Embodiment 2

[0042]Add 0.002% of the fermentation promoter in the feed, but not in the fermentation medium. Other specific fermentation process technology (medium configuration, spore culture, primary seed culture, secondary seed culture, fermentation culture and feed 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, and specifically relates to the fermentation production of gentamicin, in particular to a fermentation promoter used to increase the yield of gentamicin C1a and an adding method.Background technique[0002]Gentamicin C1a, as one of the main components of gentamicin, is an important aminoglycoside antibiotic. It is the core of a semi-synthetic new drug itilmicin, which is the first in China and possesses 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. Because the components are similar in structure and similar in physical and chemical properties, the extraction cost remains high and the market is high. The price of purity C1a remains high. Therefore, it is of great significance to the research of gentamicin C1a fermentation.[0003]In the fermentation process ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P19/48C12R1/29
CPCC12P19/485
Inventor 程国政
Owner HENAN RENHUA BIOTECH CO LTD