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A kind of method for preparing statamycin

A technology of statamycin and streptomyces, which is applied in the field of biopharmaceuticals, can solve the problems that the excellent characteristics of strains are not easy to be fully expressed, the potential of strains cannot be fully tapped, and the potency of statamycin is low, and it is beneficial to Solid-liquid separation, large increase in antibiotic production, improved extraction yield and the effect of finished product quality

Active Publication Date: 2018-06-22
ZHEJIANG HISUN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current production process of statamycin, due to the low level of fermentation, the process is not yet perfect, and the excellent characteristics of the strain are not easy to fully express, resulting in the disadvantages of low potency of statamycin, large fluctuations in output, low yield, and high cost.
Jiang Shichun et al. selected a high-yielding strain of Distalmyces (Acta Laser Biology, 2014, 23(2), 189-192) to obtain the mutant strain Streptomyces distallicus DZ206 through mutagenesis, and its yield was 1.38 times higher than that of the original strain Streptomyces distallicus D32. It provides a way to increase the production level of statamycin. Since the fermentation process has not been further optimized, the potential of Streptomyces distallicus DZ206 strains has not been fully tapped, and there is a limit to greatly increasing the production. Therefore, an efficient preparation of statamycin is sought. Work on the mycin method continues

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  • A kind of method for preparing statamycin

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Embodiment 1: the preparation of statamycin

[0072] (1) Strain: Streptomyces distallicus DZ206

[0073] (2) Preparation of slant spores and culture medium formula (%): glucose 4.5, yeast powder 1.5, sodium chloride 0.3, magnesium sulfate heptahydrate 0.05, calcium carbonate 0.2, ammonium sulfate 0.05, EDTA0.02, PH6. 2. Prepared with natural water, the volume of a 500ml triangular bottle is 50ml. Cultivation is based on sterilization at a temperature of 121-125°C and a pressure of 0.10-0.13Mpa for 30 minutes. After proper cooling, it is placed on an inclined plane for use.

[0074] Spread the spore liquid of Streptomyces distallicus DZ206, a statamycin-producing bacterium, evenly on the above-mentioned blank slope, and incubate it in a constant temperature incubator at 29±2°C for 6-12 days. After growing mature, the spores are off-white.

[0075] (3) Preparation and cultivation of shake flask seed medium

[0076] Culture medium formula (%): Glucose 2, corn steep liqu...

Embodiment 2

[0079] Embodiment 2: the preparation of statamycin

[0080] Small fermenter test

[0081] (1) See Example 1 for the preparation and cultivation of strains and slant spores

[0082] (2) Preparation of shake flask mycelia

[0083] Medium formula (%) Glucose 2, corn steep liquor 2.5, calcium carbonate 1.0, ammonium sulfate 0.1, potassium dihydrogen phosphate 0.01, pH 6.0, drinking water preparation. The capacity of a 1000ml triangular bottle is 200ml, and the culture is based on sterilization at a temperature of 121-125°C and a pressure of 0.10-0.13Mpa for 30 minutes. After cooling, the slant spores are inserted into the seed medium by the method of digging blocks, and the culture temperature is 29± In a shaker at 2°C with a rotation speed of 220 rpm, shake culture for about 40 hours, the mycelium concentration is about 12%, the appearance is light yellow, the mycelium is deeply stained under the microscope, and there are branches and segments.

[0084] (3) Ingredients and cul...

Embodiment 3

[0088] Embodiment 3: the preparation of statamycin

[0089] (1) See Example 1 for the preparation and cultivation of strains and slant spores

[0090] (2) Preparation of shake flask mycelia

[0091] Medium formula (%) Glucose 2, corn steep liquor 2.5, calcium carbonate 1.0, ammonium sulfate 0.1, potassium dihydrogen phosphate 0.01, pH 6.0, drinking water preparation. The capacity of a 1000ml triangular bottle is 200ml, and the culture is based on sterilization at a temperature of 121-125°C and a pressure of 0.10-0.13Mpa for 30 minutes. After cooling, the slant spores are inserted into the seed medium by the method of digging blocks, and the culture temperature is 29± In a shaker at 2°C with a rotation speed of 220 rpm, shake culture for about 40 hours, the mycelium concentration is about 12%, the appearance is light yellow, the mycelium is deeply stained under the microscope, and there are branches and segments.

[0092] (3) Ingredients and cultivation of seed tanks

[0093...

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Abstract

The present invention also provides a method for preparing statamycin, the method comprising the fermentation of Streptomyces capable of producing statamycin containing an available carbon source, an available nitrogen source and 3-hydroxy-4-aminobutyric acid The step of fermenting in the culture medium, and the step of adding vegetable oil to the fermentation medium in the middle of fermentation. The method has the advantages of high potency, easy extraction of the final product, etc., and overcomes the abnormal phenomena of low fermentation yield, high viscosity, paste, unclear filtration, low yield and large loss in the original process.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to a method for preparing statamycin by fermentation. Background technique [0002] Streptomycin is an antibiotic produced by Streptomyces netropsis or S.distallicus, its hydrochloride is yellow-white crystalline powder, and its molecular formula is C 22 h 27 N 9 o 4 HCL has a molecular weight of 517.975 and a melting point of 184-187°C. Soluble in water, insoluble in organic solvents. This product should be stored away from light and moisture. Stamycin has inhibitory effects on Gram-positive bacteria, fungi, and viruses, and its mechanism of action is mainly to inhibit DNA synthesis. Stamycin is mainly used for skin and mucous membrane infections caused by herpes simplex, herpes zoster, and vaccinia virus. It is also an oligopeptide antibiotic with certain anticancer activity. It can affinity with a specific sequence of DNA and recognize DNA. It is based on the expression o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/16C12R1/465
CPCC12P17/16C12R2001/465C12N1/205C12P19/56
Inventor 蒋世春滕云江连清
Owner ZHEJIANG HISUN PHARMA CO LTD