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A kind of method and fermentation medium for producing romidepsin

A fermentation medium and technology of romidepsin, applied in the field of romidepsin production, can solve the problem of low yield

Active Publication Date: 2019-01-01
SHANGHAI INST OF PHARMA IND CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to overcome the defect of low yield of romidepsin produced by the existing fermentation medium for producing romidepsin and provide a method for producing romidepsin and fermentation culture medium

Method used

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  • A kind of method and fermentation medium for producing romidepsin

Examples

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Effect test

Embodiment 1

[0035]Chromobacterium violaceum (Chromobacterium violaceum) WB968 was activated and inoculated on the slant medium (LB medium: sterilized at 121°C for 20 minutes), and the slant was placed in a constant temperature incubator at 28°C for 1 day to obtain the bacteria in the growth phase. Then the bacteria were inoculated into a 250mL shaker flask containing 30mL seed medium (glucose 1%, yeast extract 0.5%, peptone 1%, sodium chloride 0.5%), and cultured on a shaker at 30°C and 220rpm for 1 day to obtain mature The seed solution obtained was inserted into 30mL fermentation medium (glucose 2%, mannitol 2%, corn steep liquor 1.0%, casein 0.2%, soybean powder 0.5%, sodium chloride 0.5%, potassium dihydrogen phosphate 1.0%, magnesium sulfate heptahydrate 0.05%, rice oil 0.05%, pH7.0) in a 250mL shake flask, placed in a shaker at 25°C for 96 hours, the relative titer was 300%, The output of romidepsin is 600mg / L.

Embodiment 2

[0036] The method for producing romidepsin in Examples 2-23 is the same as in Example 1, except that the components and / or contents in the fermentation medium are different, and the relative potency and yield are different. Examples 2-23 The content, relative potency and yield of each component in the medium fermentation medium are shown in Table 1. Wherein, the relative potency in Example 2 is 100%. The method for producing romidepsin in Comparative Examples 1-13 is the same as that of Example 1, except that the components and / or contents in the fermentation medium are different, and the relative potency and yield are different. Comparative Examples 1-13 The contents, relative potency and yield of each component in the fermentation medium of 9 are shown in Table 2. Table 3 shows the content, relative potency and yield of each component in the fermentation medium of Comparative Examples 10-13.

[0037] In the following tables 1-3, (1): glucose (%); (2): mannitol (%); (3): co...

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Abstract

The invention discloses a romidepsin production method and a fermentation medium thereof. The fermentation medium for romidepsin production includes a carbon source, an organic nitrogen source and an inorganic phosphate; the carbon source comprises glucose and mannitol, and the organic nitrogen source comprises corn steep liquor, casein and soybean powder; the carbon source accounts for 4-10% of the weight of the fermentation medium; the organic nitrogen source accounts for 2-5% of the weight of the fermentation medium; and the inorganic phosphate accounts for 0.1-2.1% of the weight of the fermentation medium. The invention also discloses the romidepsin production method. When the fermentation medium is used in the romidepsin production, the output is increased to 500-600mg / L and is above 150-200% higher than the output realized by using fermentation media in the prior art.

Description

technical field [0001] The invention relates to a method for producing romidepsin and a fermentation medium. Background technique [0002] Romidepsin is a natural polypeptide isolated from the fermentation broth of Chromobacterium violaceum, and its molecular formula is C 24 h 36 N 4 o 6 S 2 , with a molecular weight of 540. [0003] Romidepsin is a new type of histone deacetylase (HDAC) inhibitor. HDAC is a kind of zinc ion amidase. When catalyzing histone deacetylation, zinc ion is chelated with the hydrate of oxygen on the acetyl group The excessive or abnormal regulation of HDAC leads to excessive deacetylation of histones, and the condensation of chromosomes inhibits transcription, resulting in a decrease in the expression of corresponding genes, leading to tumorigenesis. The anti-tumor mechanism of romidepsin is that after romidepsin enters the cell, its disulfide bond is reduced to a sulfhydryl group by reducing glutathione (GSH), and the sulfhydryl group can co...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P21/02C12R1/01
Inventor 胡海峰熊磊
Owner SHANGHAI INST OF PHARMA IND CO LTD
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