High-yield fermentation production method of doramectin

A technology for doramectin and a production method, applied in the field of fermentation engineering, can solve the problems of unstable fermentation level, large workload, long time consumption, etc., and achieves the improvement of the doramectin fermentation level, the improvement of the fermentation level and the reduction of production cost. Effect

Active Publication Date: 2018-08-14
HUBEI HONCH PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, domestic and foreign research methods to improve the production of doramectin mainly focus on strain selection, gene mutant strain screening, optimization of

Method used

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  • High-yield fermentation production method of doramectin
  • High-yield fermentation production method of doramectin
  • High-yield fermentation production method of doramectin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] In this example, the strain is a mutant strain of Streptomyces avermitilis, and the potency of the shake flask is 2500-3000 μg / mL.

[0038] To prepare different forms of precursor salts, cyclohexanecarboxylic acid and 3 mol / L NaOH, KOH, NH 4 React with OH solution to obtain sodium cyclohexylcarboxylate, potassium cyclohexylcarboxylate, and ammonium cyclohexylcarboxylate. After being fully dissolved in sterile water, prepare a 20% saline solution, filter and sterilize using a microfiltration membrane with a diameter of 0.22 μm, and set aside.

[0039] Different forms of precursor solutions were prepared, and cyclohexanecarboxylic acid was dissolved in 1.5 times the mass volume of methanol, ethanol, and acetone solvents, and sterilized by microfiltration membranes with a diameter of 0.22 μm before use.

[0040] Prepare different forms of precursor emulsification system, respectively use 10 times the mass of water, 2.5 times the mass of glycerol and 10 times the water, 2.5...

Embodiment 2

[0048] According to the results of Example 1, the key factors of the emulsification system to promote the fermentation of doramectin were investigated, and the precursor form added to the fermentation broth was an emulsification system composed of 0.20% cyclohexanecarboxylic acid+glycerol+water, cyclohexanecarboxylic acid + water emulsification system, 0.20% sodium cyclohexyl carboxylate+glycerol+water system, according to the method of embodiment 1, the precursor addition time is fermentation 24h, the control group adds 0.20% sodium cyclohexyl carboxylate in the culture medium after inoculation, the result As shown in table 2.

[0049] Table 2: Factors affecting the fermentation yield of doramectin in the precursor emulsification system

[0050]

[0051] As can be seen from Table 2, glycerol is stronger to Dora fermentation in the cyclohexanecarboxylic acid+glycerol+water emulsification system, and the water emulsification system of cyclohexanecarboxylic acid also has a hi...

Embodiment 3

[0053] According to the results of Example 1, the emulsification system in which the precursor form is cyclohexanecarboxylic acid+glycerol+water is selected to be added to the fermentation broth, and according to the method of Example 1, different amounts of 0.01% and 0.05% are added to the fermentation medium , 0.08%, 0.10%, 0.12%, 0.15%, 0.18%, 0.20%, 0.25%, 0.30%, 0.35%, 0.40%, 0.45%, 0.50% of the precursor, the precursor addition time is 24h of fermentation, the control group 0.20% sodium cyclohexanecarboxylate was added to the inoculated medium, and the results are shown in Table 3.

[0054] Table 3: Effects of different concentrations of emulsification system precursors on the fermentation yield of doramectin

[0055]

[0056] It can be seen from Table 3 that adding 0.3% cyclohexanecarboxylic acid+glycerol+water emulsification system in the fermentation culture can significantly increase the fermentation yield of doramectin, and the effect of low concentration and hig...

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Abstract

The invention provides a high-yield fermentation production method of doramectin. The high-yield fermentation production method comprises the following steps: dissolving a doramectin precursor into water, methanol or ethanol or dispersing the doramectin precursor into a glycerol emulsifying system so as to be convenient for disinfection and material supplementation, wherein the doramectin precursor is cyclohexanecarboxylic acid or sodium cyclohexanecarboxylate; inoculating a strain seed solution into a fermentation culture medium and fermenting; adding the precursor which accounts for 0.02 to0.08 percent of the total weight of the fermentation culture medium at the early period of fermentation for induction; adding the precursor which accounts for 0.18 to 0.22 percent of the total weightof the fermentation culture medium at the middle period of the fermentation; adding the precursor which accounts for 0.02 to 0.08 percent of the total weight of the fermentation culture medium at thelater period of the fermentation. The method is simple and effective, and can be used for rapidly improving a fermentation level of the doramectin; the production cost is reduced and extra equipment and manpower do not need to be increased; the fermentation level of the doramectin can be relatively greatly improved and the production method is relatively suitable for commercial large-scale production.

Description

technical field [0001] The invention belongs to the field of fermentation engineering, and in particular relates to a fermentation production method for increasing the yield of doramectin by optimizing the way of adding precursors. Background technique [0002] Doramectin is a macrolide insecticide synthesized by Pfizer of the United States using the avermectin Streptomyces mutant strain with cyclohexanecarboxylic acid (CHC) precursor. It has a wide range of anti-parasites and significant effects. The route of administration is easy to grasp, high bioavailability, and long drug residual period. It has been used in veterinary clinics in cattle, horses, sheep, goats, pigs, camels, dogs and other mammals. It is also a new spectrum antibiotic selamectin. However, the domestic doramectin fermentation yield is low and the production cost is high, which limits its wide application. [0003] According to literature reports (QA Mckellar, et al, 1996), the biosynthetic pathway of dor...

Claims

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Application Information

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IPC IPC(8): C12P19/62C12R1/465
CPCC12P19/62
Inventor 何福彪潘校军张文凯
Owner HUBEI HONCH PHARMA
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