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A kind of cyst fungus citrus finger and its application in regulating the microbial metabolite fidaxomicin

A technology of fidaxomicin and fidaxomicin, which is applied in the field of obtaining fidaxomicin by regulating the metabolism of microorganisms, can solve the problems of difficulty in purification and affecting the quality of medicines, and achieve production The effect of stable capacity, less homologue peaks, and less fermentation by-products

Active Publication Date: 2019-10-15
HANGZHOU HUADONG MEDICINE GRP PHARMA RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Those of ordinary skill in the art all know that the fidaxomicin fermentation product prepared by the prior art contains more impurities and by-products, and the existence of these substances will bring great difficulty to subsequent purification. Impurities that are difficult to remove in the process will seriously affect the quality of the final drug

Method used

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  • A kind of cyst fungus citrus finger and its application in regulating the microbial metabolite fidaxomicin
  • A kind of cyst fungus citrus finger and its application in regulating the microbial metabolite fidaxomicin
  • A kind of cyst fungus citrus finger and its application in regulating the microbial metabolite fidaxomicin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: The culture, physiological and biochemical characteristics and carbon source utilization of the strain with the preservation number CCTCC NO: M 2017311

[0037] 1. The morphological characteristics of the cultured strain with the preservation number CCTCC NO: M 2017311

[0038] The strain with the preservation number CCTCC NO: M 2017311 was inoculated on ISP2 (yeast extract malt extract powder agar) medium, cultured at 30°C for 10-14 days, and the morphological characteristics of the colonies were observed and described.

[0039] Observation found that the colony grew abundantly, with a diameter of 1-2 mm in 14 days; the colony was nearly round in the early stage of culture, and irregularly protruded at the edge and depressed in the center in the later stage of culture; the color of mycelium was light orange to light pink, and no secretions and soluble pigments were produced.

[0040] 2. The preservation number is CCTCC NO: M 2017311 strain physiological and ...

Embodiment 2

[0050] Embodiment 2: Fermentation culture prepares Fidaxomycin

[0051] The strain with the preservation number CCTCC NO: M 2017311 was used.

[0052] 1. Strain cultivation and storage

[0053] Solid medium: glucose 1g, soluble starch 2g, yeast extract powder 1g, acid hydrolyzed casein 0.5g, agar 2g, add water to 100mL, adjust pH to 7.0.

[0054] Solid culture method: the strain is inoculated on a solid medium slant, and cultured at 30°C for 8-10 days.

[0055] After the solid culture is over, place it on an inclined plane at 4-10°C and refrigerate it for later use.

[0056] 2. Shake flask seed culture

[0057] Medium: glucose 1g, corn starch 0.5g, potato starch 0.5g, yeast powder 1g, soybean peptone 1.5g, beef extract 2g, soybean cake powder 0.5g, CaCO 3 0.4g, add water to 100mL, pH7.0.

[0058] Filling volume: 100mL medium in a 500mL Erlenmeyer flask, sterilized at 121°C for 30min.

[0059] Inoculum size: 5% (V / V) 30% glycerol mycelia cryovial

[0060] Cultivation tem...

Embodiment 3

[0076] Embodiment 3: Fermentation culture prepares Fidaxomycin

[0077] (1) Fermentation of Fidaxomicin

[0078] The strain with the preservation number CCTCC NO: M 2017311 was used.

[0079] Shake flask seed culture: Each 100mL medium contains 0.5g of glucose, 0.5g of corn starch, 5g of soybean peptone, 0.2g of yeast powder, 1.5g of beef extract, 1g of soybean cake powder, and CaCO 3 0.1g, the rest is water, the pH is natural. Insert 5% (V / V) 30% glycerol mycelia freezing tube, 220 rpm, and culture at 28° C. for 2 days to obtain seed liquid.

[0080] Seed tank culture: every 100mL medium contains 0.5g of glucose, 0.5g of yeast powder, 1g of corn starch, 5g of soybean peptone, 1.5% of beef extract, 1g of cottonseed powder, 1g of corn steep liquor powder, KH 2 PO 4 0.5g, CaCO 3 0.1g, the rest is water, the pH is natural. Seed inoculation amount 0.1% (V / V), 150 rpm, 30° C. for 4 days.

[0081] Fermentation tank culture: every 100mL medium contains 1g of glucose, 3g of ...

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Abstract

The invention discloses a Dactylosporangium aurantiacum FID1307 and its application. The strain is preserved by the China Center for Typical Culture Collection, the preservation number is CCTCC NO: M2017311, and the preservation date is: June 07, 2017 day. The invention also discloses a method for fermenting and preparing fidaxomicin from the bacterial strain. The fermentation process provided by the invention has been proved by large-scale production practice to have stable fermentation and few by-products, which greatly reduces the difficulty of post-extraction, is suitable for large-scale industrial production, and obtains high-quality fidaxomicin products.

Description

technical field [0001] The invention relates to a microorganism and its application in the field of pharmacy, in particular to the application of Fidaxomycin obtained by regulating the metabolism of microorganisms by Cystia citrus. Background technique [0002] Fidaxomicin (trade name Dificid, previously used as OPT-80, PAR-101), is a macrolide antibiotic with an 18-membered ring structure, which can be produced by Dactylosporangium aurantiacum subspecie hamdenensis ) obtained by fermentation, specifically produced by Actinomycetes NRRL 18085. Jucheng means that the products obtained from the fermentation of cystic bacteria are a family of products that are very similar in structure to fidaxomicin, called tiacumicins (tiacumicins), and are called tiacumicins A, B, C, D, E and F. Fidaxomicin is tiacumicin B in the R configuration and has a novel mechanism of action (the structural formula is shown below). [0003] [0004] Fidaxomycin was approved by the US FDA in May 2...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N1/20C12P19/62C12R1/01
CPCC12P19/62C12N1/205C12R2001/01
Inventor 陈晓霞王蓓赵万忠冯国栋谢海军
Owner HANGZHOU HUADONG MEDICINE GRP PHARMA RES INST
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