Method for producing 11alpha-hydroxy-4-ene-3,17-androstanedione

A technology for the production of androstadione and its production method, which is applied in the field of transformation of steroid drug intermediates, can solve the problems of insufficient fermentation control and optimization, reduced competitiveness, and increased costs, so as to shorten the production cycle and be beneficial to environmental protection , the effect of improving the utilization rate

Active Publication Date: 2018-05-29
河北远大九孚生物科技有限公司
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

Although the microbial fermentation method is beneficial to environmental protection, it has the disadvantages of low feed amount and low yield, and due to insufficient c

Method used

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  • Method for producing 11alpha-hydroxy-4-ene-3,17-androstanedione
  • Method for producing 11alpha-hydroxy-4-ene-3,17-androstanedione
  • Method for producing 11alpha-hydroxy-4-ene-3,17-androstanedione

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Embodiment 1

[0086] Example 1 Production of 11α-hydroxy-4-ene-3,17-androstadione using microbial fermentation

[0087] 1.1 Production of spore eggplant-shaped bottle

[0088] Inoculate the preserved seeds of Aspergillus ochraceus ATCC18500 on a solid slant medium and place them in an incubator at 28°C. After culturing for 7-10 days, the spores on the surface of the slant are off-white, and the back of the slant is dark red with wrinkles; then, put Refrigerate at 4 degrees for later use.

[0089] The solid slant medium includes the following components: glucose 20g / L, peptone 1.0g / L, malt extract 20g / L, agar powder 20g / L, pH adjusted to 5.5-6.0 before disinfection

[0090] 1.2 Level 1 seed tank

[0091] Shovel the spores in step 1 into sterile water, then inoculate them in a primary seed tank for cultivation; after inoculation, the rotational speed of the primary seed tank is 50-100rpm, the air ratio is 0.3-0.6, and the culture cycle is 35-40 Hour;

[0092] Wherein, the first-level see...

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Abstract

The present invention provides a method for producing 11alpha-hydroxy-4-ene-3,17-androstanedione. The method comprises use of fungi to convert substrate 4-ene-3,17-androstenedione to the 11alpha hydroxy-4-ene-3,17-androstenedione, and includes the following steps: 1) collecting spores of a desired specie, and performing seed culture; 2) placing the seeds obtained in the step 1) in a conversion tank, and using a conversion culture medium to ferment and culture; 3) crushing the substrate, and beating with a 30 to 60% (v/v) aqueous ethanol solution to form a paste; 4) continuously adding the substrate of the step 3) in batches into the conversion culture medium in the conversion tank of the step 2) for 2 to 5 times, wherein in each time of adding, the amount of the added substrate is 1-3% (w/v) of the volume of the fermented liquid in the conversion tank, and the time for each time of adding is 4 to 5 hours. Compared with the prior art, the method provided by the invention improves the feeding amount of the substrate, the utilization rate and the conversion time greatly shorten the production cycle, and the method is an efficient and environmentally friendly production method.

Description

technical field [0001] The invention belongs to the technical field of microbial transformation, and relates to a method for transforming steroidal drug intermediates, more specifically to converting 4-ene-3,17-androstadione into 11α-hydroxyl-4-ene by microbial fermentation - 3,17-androstanedione method. Background technique [0002] Microorganisms can selectively modify or transform the molecular structure of steroids, which is catalyzed by enzymes produced by microorganisms. In 1952, biochemist D.H. Peterson and microbiologist H.C. Murray of Upjohn Pharmaceuticals in the United States discovered that Rhizopus aureus can hydroxylate the 11-carbon position of progesterone to generate 11α-hydroxyprogesterone, and scientists successively discovered Some species of bacteria, fungi, and actinomycetes can change the molecular structure of steroid compounds with a certain structure at a certain position. This enzymatic reaction has strict substrate specificity, and generally one...

Claims

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Application Information

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IPC IPC(8): C12P33/10C12R1/66C12R1/845
CPCC12P33/10
Inventor 李哲余伟李佳刘美龙
Owner 河北远大九孚生物科技有限公司
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