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Fermentation culture medium for biologically synthesizing 7alpha, 15alpha-dihydroxyandrostenolone

A technology of hydroxyandrostenolone and fermentation medium, which is applied in the direction of microorganism-based methods, fermentation, microorganisms, etc., can solve the problems of low conversion efficiency, low substrate feeding concentration, low conversion rate, etc., and achieve low conversion rate. High, solve the effect of low substrate feeding concentration and reduce the cost of industrial production

Inactive Publication Date: 2012-05-09
SHANGHAI INST OF PHARMA IND CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the feed concentration of the substrate in the two methods is very low, only 1g / L, so the conversion efficiency is very low, and the cost of industrial production is very high
Shang Ke et al. (Chinese Journal of Medical Biotechnology Applications. 2, 30-34, 2004) reported that Colletotrichum lini AS3.4486 can convert II into I, but the substrate concentration is very low, only 2g / L. The low yield is only 58.8%, and the conversion rate is also low, about 70%
It can be seen that the existing conversion process cannot efficiently synthesize I, and a more effective conversion process is urgently needed to increase the feed concentration and conversion rate of the substrate to reduce production costs

Method used

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  • Fermentation culture medium for biologically synthesizing 7alpha, 15alpha-dihydroxyandrostenolone
  • Fermentation culture medium for biologically synthesizing 7alpha, 15alpha-dihydroxyandrostenolone
  • Fermentation culture medium for biologically synthesizing 7alpha, 15alpha-dihydroxyandrostenolone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] culture medium

[0026] Slant medium: PDA medium (200g potato juice 1000ml, glucose 20g, agar 20g), sterilized at 121°C for 20min.

[0027] Seed medium: peanut cake powder 10g / L; dextrin 30g / L; KCl 1g / L; (NH 4 ) 2 HPO 4 1g / L; K 2 HPO 4 1g / L; MgSO 4 ·6H 2 O1g / L. pH5.5, sterilized at 121°C for 20min.

[0028] Fermentation medium: yeast extract 10g / L; maltodextrin 35g / L; sunflower oil 5g / L; KCl 1g / L; (NH 4 ) 2 HPO 4 1g / L; K 2 HPO 4 1g / L; MgSO 4 ·6H 2 O1g / L. pH5.5, sterilized at 121°C for 20min.

[0029] Transformation process: Place the slant of the inoculated bacteria in a constant temperature incubator at 28°C, cultivate for 6 days to obtain mature spores, and then inoculate the mature spores in a 250ml shaker flask containing 30ml of seed medium, at 30°C, 230rpm Cultivate on a shaker for 3 days to obtain mature seeds. The seeds obtained are inserted into a 750ml shaker flask with 100ml fermentation medium with 10% inoculum size, placed at 30°C, 230r / min...

Embodiment 2

[0031] The slant medium and seed medium are the same as in Example 1.

[0032] Fermentation medium: peptone 20g / L; maltodextrin 30g / L; lard 5g / L; KCl1g / L; (NH 4 ) 2 HPO 4 1g / L; K 2 HPO 4 1g / L; MgSO 4 ·6H 2 O1g / L. pH5.5, sterilized at 121°C for 20min.

[0033] The conversion process is the same as in Example 1, and the final conversion rate is 85.1%.

Embodiment 3

[0035] The slant medium and seed medium are the same as in Example 1.

[0036] Fermentation medium: beef extract 30g / L; dextrin 20g / L; lecithin 1g / L; KCl 1g / L; (NH 4 ) 2 HPO 4 1g / L; K 2 HPO4 1g / L; MgSO 4 ·6H 2 O1g / L. pH5.5, sterilized at 121°C for 20min.

[0037] The conversion process is the same as in Example 1, and the final conversion rate is 85.3%.

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Abstract

The invention discloses a fermentation medium for biosynthesis of 7 alpha-dihydroxy androstene alcohol ketone and 15 alpha-dihydroxy and rostene alcohol ketone by taking flax colletotrichum (Colletotrichum lini AS 3.4) as strain, consisting of organic nitrogen sources, carbon sources, inorganic salts and metal ions. The invention is characterized in that: the organic nitrogen sources are peptones, yeast extracts, beef extracts and yeast extract pastes. When a product I is synthesized by adoption of the fermentation medium of the invention, substrate feed concentration can reach 8 grams per liter (substrate weight / fermentation broth volume) and conversion ratio can reach 85 percent, thereby the invention can well solve the defects of low substrate feed concentration and low conversion ratio of the prior art, and then industrial production cost of the product I is reduced.

Description

technical field [0001] The invention relates to a microbial steroid transformation medium, in particular to a microbial fermentation medium for biosynthesizing 7α, 15α-dihydroxyandrostenolone. Background technique [0002] Steroid intermediates are often used in the production of various clinical drugs. 7α, 15α-dihydroxyandrostenolone (its structure is as follows formula I) [0003] [0004] It is an important steroid intermediate, which can be used in the synthesis of various drugs such as lactone aldosterone receptor antagonists, diuretics and gynecological drugs. For example, I is an important intermediate in the synthesis of drospirenone, the active ingredient of the oral contraceptive drug Yasmin. [0005] Microbial transformation plays an important role in the synthesis of steroid drugs. Several important steroid microbial transformation reactions such as hydroxylation, dehydrogenation and side chain degradation have become important methods for the industrial pro...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P33/06C12N1/14C12R1/645
Inventor 胡海峰陶荣盛张琴
Owner SHANGHAI INST OF PHARMA IND CO LTD
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