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Preparation method of 7-O-demethylated rapamycin

A technology of methyl rapamycin and seeds, which is applied in the field of preparation of 7-O-desmethyl rapamycin, can solve the problems of inconvenience and low content of 7-O-desmethyl rapamycin, To achieve the effect of abundant raw materials, high output and simple operation of the preparation process

Pending Publication Date: 2022-04-22
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The prior art has a large number of reports on the synthesis method of rapamycin, but there are few reports on the biosynthesis method for 7-O-desmethyl rapamycin. The content of kirapamycin is low, which brings inconvenience to the study of this impurity

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Incline medium: yeast powder 10g / L, corn starch 10g / L, glucose 10g / L, agar powder 20g / L, calcium carbonate 1g / L.

[0043] Primary seed medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor powder 6g / L, peanut protein powder 4g / L, cornstarch 10g / L, calcium carbonate 1g / L.

[0044] Secondary seed medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor dry powder 6g / L, peanut protein powder 4g / L, corn starch 10g / L, bubble enemy DF-104 1%, calcium carbonate 1g / L L.

[0045] Seed tank medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor powder 6g / L, peanut protein powder 4g / L, corn starch 10g / L, foam enemy DF-104 2%, calcium carbonate 1g / L .

[0046] Fermentation medium: cottonseed protein powder 20g / L, peanut protein powder 4g / L, dextrin 10g / L, glycerin 80g / L, corn steep liquor powder 6g / L, yeast extract 10g / L, L-leucine 4g / L, piperidine-2-carboxylic acid 30g / L, KH 2 PO 4 1g / L, SAG630 1.9g / L, MgSO 4 ·7H 2 O1...

Embodiment 2

[0054] Incline medium: yeast powder 10g / L, corn starch 10g / L, glucose 10g / L, agar powder 20g / L, calcium carbonate 1g / L.

[0055] Primary seed medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor powder 6g / L, peanut protein powder 4g / L, cornstarch 10g / L, calcium carbonate 1g / L.

[0056] Secondary seed medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor dry powder 6g / L, peanut protein powder 4g / L, corn starch 10g / L, bubble enemy DF-104 1%, calcium carbonate 1g / L L.

[0057] Seed tank medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor powder 6g / L, peanut protein powder 4g / L, corn starch 10g / L, foam enemy DF-104 2%, calcium carbonate 1g / L .

[0058] Fermentation medium: cottonseed protein powder 20g / L, peanut protein powder 4g / L, dextrin 10g / L, glycerin 80g / L, corn steep liquor powder 6g / L, yeast extract 10g / L, L-leucine 4g / L, piperidine-2-carboxylic acid 30g / L, KH 2 PO 4 1g / L, SAG630 1.9g / L, MgSO 4 ·7H 2 O ...

Embodiment 3

[0066] Incline medium: yeast powder 10g / L, corn starch 10g / L, glucose 10g / L, agar powder 20g / L, calcium carbonate 1g / L.

[0067] Primary seed medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor powder 6g / L, peanut protein powder 4g / L, cornstarch 10g / L, calcium carbonate 1g / L.

[0068] Secondary seed medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor dry powder 6g / L, peanut protein powder 4g / L, corn starch 10g / L, bubble enemy DF-104 1%, calcium carbonate 1g / L L.

[0069] Seed tank medium: cottonseed protein powder 20g / L, glucose 10g / L, corn steep liquor powder 6g / L, peanut protein powder 4g / L, corn starch 10g / L, foam enemy DF-104 2%, calcium carbonate 1g / L .

[0070] Fermentation medium: cottonseed protein powder 20g / L, peanut protein powder 4g / L, dextrin 10g / L, glycerin 80g / L, corn steep liquor powder 6g / L, yeast extract 10g / L, L-leucine 4g / L, piperidine-2-carboxylic acid 30g / L, KH 2 PO 4 1g / L, SAG630 1.9g / L, MgSO 4 ·7H 2 O ...

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PUM

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Abstract

The invention belongs to the technical field of biology, and particularly relates to a preparation method of 7-O-demethylated rapamycin. According to the method, actinoplanes are used as starting strains, and the biosynthesis of the increased 7-O-demethylated rapamycin is realized through shake flask fermentation or fermentation tank fermentation by selecting different types of cosolvents and different amino acids corresponding to different periods of addition. The preparation process of the 7-O-demethylated rapamycin is simple to operate, short in fermentation period and high in directionally synthesized purity and yield, and provides abundant raw materials for impurity research of the rapamycin.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a preparation method of 7-O-desmethylrapamycin. Background technique [0002] Rapamycin (sirolimus) is a macrolide antibiotic produced by Streptomyces hygroscopicus isolated by Veniza et al. in 1975. After years of research, rapamycin has been developed into a potent immunosuppressant for clinical use. At the same time, using rapamycin as a precursor, some derivatives with novel structures chemically modified and synthesized have been found to have new therapeutic effects on immunosuppression, anti-cancer, anti-Parkinson syndrome and AIDS, among which the synthetic Temsirolimus, Everolimus and AP23573 have been clinically studied as new anti-tumor targeted drugs, and rapamycin has broad prospects in the field of medical applications. [0003] During the fermentation process, Streptomyces hygroscopicus not only produces the main product sirolimus, but also synthesizes so...

Claims

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Application Information

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IPC IPC(8): C12P17/18C12N1/20C12R1/045
CPCC12P17/18C12N1/20
Inventor 张贵民马印虎朱兵峰刘存磊刘忠
Owner LUNAN PHARMA GROUP CORPORATION
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