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Streptomycete and use thereof

A Streptomyces and strain technology, applied in bacteria, microorganisms, biochemical equipment and methods, etc., can solve the problems of high solvent consumption and energy consumption, complex extraction and purification process, low fermentation unit, etc., to achieve stable production capacity, fermentation Excellent performance and less fermentation by-products

Active Publication Date: 2011-11-16
HANGZHOU HUADONG MEDICINE GRP PHARMA RES INST +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

General tacrolimus-producing bacteria have very low fermentation units and more fermentation by-products, resulting in more complicated post-extraction work
The patent USP4894366 published by Okuhara et al. mentioned the extraction and purification process of tacrolimus. The fermentation broth of Streptomyces tsukubaensis No.9993 strain was filtered to obtain the bacterial residue, which was extracted with acetone, and the extract was adsorbed and desorbed by HP20 resin. The desorption solution was concentrated, extracted with ethyl acetate, and the ethyl acetate phase was concentrated to obtain an oily crude product, which was then purified by several times of special silica gel chromatography, and finally crystallized and recrystallized in acetonitrile to obtain tacrolimus, The whole extraction and purification process is very complicated, especially after several times of chromatography with special silica gel, it is difficult to operate in production, the consumption of solvent and energy is high, and the yield of finished product is low

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: The culture characteristics of the bacterial strain whose preservation number is CCTCC NO.M207201

[0026] The strain with the preservation number of CCTCC NO.M207201 was inoculated in the culture medium of Gao Shi No. 1, glucose asparagine, etc. for observing the morphological characteristics. Cultivate at 28°C for a certain period of time for 5, 7, and 10 days, observe and describe.

[0027] Colony characteristics of strains with preservation number CCTCC NO.M207201 on various media

[0028] culture medium

[0029] Potato Dip Agar

Embodiment 2

[0030] Example 2: Physiological and biochemical characteristics

[0031] Physiological and biochemical properties used standard methods in the classification of Streptomyces.

[0032] The physiological and biochemical reactions of the strain with the preservation number CCTCC NO.M 207201 are as follows: gelatin can be liquefied on gelatin medium, milk can be peptonized, milk cannot be coagulated, starch hydrolysis is negative, cellulose is not used, and nitrate reduction is negative.

Embodiment 3

[0033] Example 3: Carbon source utilization

[0034] Using the method recommended by the International Streptomyces Program (ISP), the carbon source utilization experiment used ISP9 as the basal medium, cultured at 28°C for 3 to 7 days, and observed the utilization of various carbon sources tested by the strains.

[0035] When the strain with the preservation number CCTCC NO.M 207201 grows, it can make good use of glycerin and maltose, but not use xylose, fructose, rhamnose, sucrose, raffinose, inositol, sorbitol, and arabinose.

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PUM

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Abstract

The invention discloses a streptomycete and the application thereof. The strain of the streptomycete is collected in China Center for Type Culture Collection (CCTCC); the collection number of the strain is CCTCC No. M 207201; and the collection date of the strain is Dec. 14, 2007. The invention further discloses a method for using the strain to ferment and prepare Tacrolimus. The fermentation process provided by the invention is tested in shake flasks and 10 tons of fermentation cylinders. The fermentation process has the advantages of stable production capacity, high fermentation unit, less byproducts of fermentation, and suitability for industrial production. In addition, the fermentation process reduces the difficulty of post-extraction.

Description

technical field [0001] The present invention relates to a novel microorganism and its use and application, in particular to a streptomyces and its application in the preparation of tacrolimus. Background technique [0002] Immunosuppressants are used to prevent rejection in organ transplantation, that is, to interfere with the receptor's recognition of foreign antigens and the removal of non-self cells. Since the first successful kidney transplant between identical twins in 1954, there have been many major breakthroughs in medical science research on organ transplantation over the past 40 years. In 1978, the clinical use of cyclosporine A (cyclosporine A) opened up a new era for organ transplantation. The 2-year survival rate of most patients with kidney transplantation has exceeded 80%, and the survival rate of patients has also improved. [0003] Tacrolimus (also known as FK506) is a biologically active substance produced by Streptomyces with a high degree of immunosuppr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N1/20C12P17/18C12R1/465
Inventor 朱健谢祥茂陈俊勇陈晓霞许永峰
Owner HANGZHOU HUADONG MEDICINE GRP PHARMA RES INST