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Method for producing mycophenolic acid from penicillium brevicompactum by high-efficiency accumulation

A technology of mycophenolic acid and Penicillium, applied in the field of high-efficiency cumulative production of mycophenolic acid by using Penicillium brevisdense, which can solve the problems of long cycle and no significant increase in production, and achieve the effect of high production

Active Publication Date: 2011-07-20
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the current literature reports, the batch fermentation method is adopted. Xu Zhinan et al. studied that the spores of Penicillium brevismis were immobilized on a rotating fiber bed fermenter (RFB) for batch fermentation, but the yield was not significantly improved after a long cycle, while flow-through There is almost no feeding method

Method used

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  • Method for producing mycophenolic acid from penicillium brevicompactum by high-efficiency accumulation
  • Method for producing mycophenolic acid from penicillium brevicompactum by high-efficiency accumulation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] The slant was cultured in PDA medium for 10 days and placed in a 4°C refrigerator to store the slant. Get the slanted seeds and use 30% glycerol to elute the spores to form a spore suspension, and 2% are inoculated into the seed shake flask medium (g / L): peptone 2.0, yeast extract 1.0, starch 1.0, glucose (C 6 h 12 o 6 ·H 2 O) 10.0, pH 6.5. Cultivate for 72 hours under the conditions of 28° C. and a rotating speed of 220 r / min, and inoculate 10% of the inoculum size into a 7L fermenter according to the volume of the medium. In the initial stage of fermentation, an optimized fermentation medium (g / L): glucose (C 6 h 12 o 6 ·H 2 O) 100.0, glycine (C 2 h 5 NO 2 ) 14.6, potassium dihydrogen phosphate (KH 2 PO 4 )3.0, magnesium sulfate (MgSO 4 ·7H 2 O) 1.0, Methionine (C 5 h 11 o 2 NS) 0.5, distilled water as the solvent, pH 4.6, the carbon and nitrogen sources were sterilized separately, and an appropriate amount of foam enemy was added.

[0023] The fermen...

Embodiment 2

[0025] The slant was cultured in PDA medium for 10 days and placed in a 4°C refrigerator to store the slant. Get the slanted seeds and use 30% glycerol to elute the spores to form a spore suspension, and 2% is inoculated into the seed shake flask medium (g / L): peptone 2.0, yeast extract 1.0, starch 1.0, glucose (C 6 h 12 o 6 ·H 2 O) 10.0, pH 6.5. Cultivate for 72 hours under the conditions of 28° C. and a rotating speed of 220 r / min, and inoculate 10% of the inoculum size into a 7L fermenter according to the volume of the medium. In the initial stage of fermentation, an optimized fermentation medium (g / L): glucose (C 6 h 12 o 6 ·H 2 O) 150, glycine (C 2 h 5 NO 2 ) 14, potassium dihydrogen phosphate (KH 2 PO 4 )2.0, magnesium sulfate (MgSO 4 ·7H 2 O) 0.5, methionine (C 5 h 11 o 2 NS) 1.0, distilled water as the solvent, pH 4.4, the carbon and nitrogen sources were sterilized separately, and an appropriate amount of foam enemy was added.

[0026]Control the ferm...

Embodiment 3

[0028] The slant was cultured in PDA medium for 10 days and placed in a 4°C refrigerator to store the slant. Get the slanted seeds and use 30% glycerol to elute the spores to form a spore suspension, and 2% is inoculated into the seed shake flask medium (g / L): peptone 2.0, yeast extract 1.0, starch 1.0, glucose (C 6 h 12 o 6 ·H 2 O) 10.0, pH 6.5. Cultivate for 72 hours under the conditions of 28° C. and a rotating speed of 220 r / min, and inoculate 10% of the inoculum size into a 7L fermenter according to the volume of the medium. In the initial stage of fermentation, an optimized fermentation medium (g / L): glucose (C 6 h 12 o 6 ·H 2 O) 100.0, glycine (C 2 h 5 NO 2 ) 15, potassium dihydrogen phosphate (KH 2 PO 4 )4.0, magnesium sulfate (MgSO 4 ·7H 2 O) 0.5, methionine (C 5 h 11 o 2 NS) 0.5, distilled water as the solvent, pH 4.8, the carbon and nitrogen sources were sterilized separately, and an appropriate amount of foam enemy was added.

[0029] Control the f...

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Abstract

The invention relates to a method for producing mycophenolic acid from penicillium brevicompactum by high-efficiency accumulation. The method comprises the following steps of: inoculating 2wt% of penicillium brevicompactum in content onto a potato dextrose agar (PDA) inclined plane, controlling the temperature at 28DEG C, activating and culturing for 72hours; and then, inoculating the activated penicillium brevicompactum into a fermentation tank, fermenting and culturing by an optimized glucose-glycine liquid nutrient medium, controlling the temperature at 28DEG C, and fermenting to obtain mycophenolic acid. Compared with the prior art, the fermentation period of the method provided by the invention is within 240 hours, and the maximum yield can achieve 5.0g / L which is improved by about 30% compared with batch fermentation. The fermentation strategy of optimizing the carbon-nitrogen ratio, supplementing feed, adjusting the pH by sections and feeding back feed supplement is simple to control, has higher yield of mycophenolic acid, and has wider industrialized application prospect.

Description

technical field [0001] The invention relates to a method for producing mycophenolic acid, in particular to a method for efficiently accumulating and producing mycophenolic acid by using Penicillium brevisdense. Background technique [0002] Myhophenolc acid (MPA) is an antibiotic produced by Penicillium brevicompactum which has antifungal, antitumor and immunosuppressive effects. MPA is a reversible inhibitor of hypoxanthine mononucleotide dehydrogenase, which can selectively inhibit the activity of lymphocytes. Its 2-ethyl ester derivative - mycophenolate mofetil (MMF) is a new generation of immune Inhibitors have shown good application prospects in the treatment of clinical organ transplantation and autoimmune diseases. MPA is used as a precursor compound for synthesizing MMF, and it is very important for production enterprises to improve the industrialization level of MPA. [0003] Most of the large-scale industrial production of modern antibiotics has changed from trad...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P17/04C12R1/81
Inventor 孙爱友魏东芝董玉国王丽华徐瑞蒋文彪
Owner EAST CHINA UNIV OF SCI & TECH
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