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Solid-state fermentation method of mycophenolic acid

A solid-state fermentation, mycophenolic acid technology, applied in microorganism-based methods, fermentation, biochemical equipment and methods, etc., can solve problems such as affecting mass transfer and heat transfer efficiency, increasing system complexity, and easy to shrink and agglomerate. , to achieve the effect of being beneficial to mass and heat transfer, environmental protection and reducing emissions

Inactive Publication Date: 2009-01-21
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 O 1g, MnSO 4 ·7H 2 O 760mg, boric acid 56mg, CaCl 2 2H 2 O100mg, CuSO 4 ·5H 2 O 25mg, ammonium molybdate 19mg, ZnSO 4 ·5H 2 O 200mg, L-Asparagi...

Embodiment 2

[0024] Add 10g of bran into 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 shake flask, fill 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, 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, comprising the following steps: firstly, subcultured penicillium is inoculated into a seed culture medium for culture and then inoculated into a secondary seed culture medium for culture, so as to obtain secondary seed solution; and secondly, 0 to 2 portions of non-inert vector and 0.2 to 3 portions of inert vector are added into a container in mass portion and uniformly mixed, and then added with distilled water so as to make the relative humidity in the container be between 65 and 95 percent; and the mixture is sterilized for 0.5 to 1.5 hours, cooled until the temperature is between 22 and 28 DEG C, inoculated with 0.2 to 2 mass portions of the secondary seed solution and cultured for 90 to 360 hours at a temperature of between 24 and 26 DEG C and with the relative humidity between 70 and 95 DEG C. The method has low energy consumption, low investment and low pollution. Moreover, the culture medium in the method can not be shrunk and hardened, thereby the method is favorable for mass transfer and heat transfer; and the inert vector can be reused, thereby reducing the discharge amount of solid waste residue and being favorable for 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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IPC IPC(8): C12P17/04C12R1/80C12R1/81
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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