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Solid state fermentation method of mycophenolic acid

A technology of solid-state fermentation and mycophenolic acid, applied in the direction of microorganism-based methods, fermentation, biochemical equipment and methods, etc., can solve problems affecting mass transfer and heat transfer efficiency, increasing system complexity, easy shrinkage and agglomeration, etc. , to achieve the effects of mass and heat transfer, environmental protection and emission reduction

Inactive Publication Date: 2011-12-21
天津北洋百川生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As a part of microbial nutrients, solid phase carriers participate in the growth and metabolism of cells. Therefore, during the growth of microorganisms, these solid phase carriers are easy to shrink and agglomerate, reducing porosity, affecting mass transfer and heat transfer efficiency during fermentation, and increasing system complexity

Method used

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  • Solid state fermentation method of mycophenolic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Cultivation of bacteria and seeds

[0021] The strain used is Penicillium brevicompactum P. brevicompactum, which is a single spore isolated from Penicillium brevicompactum, which is usually stored in potato dextrose agar (PDA) medium or spores are stored in glycerol tubes and stored in- 80°C refrigerator.

[0022] The strains were subcultured from fresh Potato Dextrose Agar (PDA) slant at a culture temperature of 28±1°C. After 8 days, the spores on the slant were washed with 10ml of normal saline containing 0.01% sterile Tween, and 5ml of bacterial suspension was taken. The solution is inserted into a 250ml shake flask, and 50ml of seed medium is installed inside, and the ingredients (g / L): 10 glucose, 5 corn steep liquor, 10 oat flour, 40 tomato paste, 10ml nutrient additive solution, and it consists of: FeSO 4 ·5H 2 O1g, MnSO 4 ·7H 2 O760mg, boric acid 56mg, CaCl 2 2H 2 O100mg, CuSO 4 ·5H 2 O25mg, ammonium molybdate 19mg, ZnSO 4 ·5H 2 O200mg, L-asparagine 1...

Embodiment 2

[0024] Add 10g of bran to a 250ml shake flask, fill it with distilled water so that the initial cultivation humidity reaches 70%, then sterilize the shake flask at 121°C for 1h, wait for the shake flask to cool to 25°C, insert 5ml of the secondary seeds prepared in Example 1 The solution was fully mixed, and the shaker flask was placed in an environmental chamber for cultivation at a cultivation temperature of 25±1°C and a relative humidity (RH) of 80±5%, for 8 days and sampling once a day.

Embodiment 3

[0026] Add 7g of bran and 3g of polyurethane foam into a 250ml shaker flask, fill with distilled water so that the initial cultivation humidity reaches 70%, then sterilize the shaker flask at 121°C for 1h, wait for the shaker flask to cool to 25°C, and insert 5ml of Example 1 The prepared secondary seed liquid was fully mixed, and the shake flask was placed into an environmental chamber for cultivation at a cultivation temperature of 25±1° C. and a relative humidity (RH) of 80±5%, and samples were taken once a day.

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Abstract

The invention discloses a method for solid-state fermentation of mycophenolic acid, which comprises the following steps: (1) inserting the subcultured Penicillium on a seed medium for cultivation, and then inserting it into a secondary seed medium for cultivation Cultivate to obtain the secondary seed liquid; (2) add 0-2 parts of non-inert carrier and 0.2-3 parts of inert carrier in parts by mass to a container, mix well, add distilled water, make the relative humidity in the container be 65% ~95%, sterilized for 0.5~1.5h, cooled to 22~28°C, inserted 0.2~2 parts by mass of the secondary seed solution, and cultivated at 24~26°C and relative humidity of 70%~95% for 90 ~360 hours. The method of the invention has low energy consumption, small investment and less pollution. Moreover, the culture medium in the method of the invention will not collapse and become hard, which is beneficial to mass transfer and heat transfer, and because the inert carrier can be used repeatedly, the emission of solid waste residue is reduced, which is beneficial to environmental protection.

Description

technical field [0001] The invention relates to a fermentation method of mycophenolic acid, in particular to a solid-state fermentation method of mycophenolic acid. Background technique [0002] Mycophenolic acid (also known as mycophenolic acid, English name mycophenolic acid, abbreviated as MPA) was discovered in 1896. It was originally isolated from the culture of Penicillium and is the third generation of immunosuppressant mycophenolate mofetil. mofetil, the precursor of MMF), has antibacterial, antifungal, anticancer and antiviral activities. The 2-ethyl ester derivative MMF of MPA is an antibiotic with immunosuppressive effect approved by the US Food and Drug Administration FDA in October 1998. It is mainly used for the prevention of organ rejection after kidney, liver and heart transplantation. It can be used in combination with cyclosporin (CsA) to reduce the dose and toxicity of the latter. Currently, MMF has a market worth more than a billion dollars a year. Oth...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P17/04C12R1/81C12R1/80
Inventor 张文博乔长晟黄皓陈娜
Owner 天津北洋百川生物技术有限公司
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