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Production method of high-ring-opening-rate lovastatin

A technology of lovastatin and a production method, which is applied to the production field of lovastatin with high ring opening rate, can solve the problems of difference in hydroxyesterase ability, unstable lipid-lowering effect of ring-closed lovastatin and the like, and achieves the effect of improving the ring opening rate

Inactive Publication Date: 2015-06-24
山东中惠生物科技股份有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Moreover, there are significant individual differences in the ability of hydroxyesterase in the human body, and some people do not even have it, which causes the instability of the lipid-lowering effect of closed-loop lovastatin

Method used

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  • Production method of high-ring-opening-rate lovastatin
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  • Production method of high-ring-opening-rate lovastatin

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Preliminary screening of mutagenized Monascus strains by confrontation culture of Aspergillus nidulans

[0032] Wash the spores from the growth slant of the initial strain with physiological saline to obtain a spore suspension, inoculate the seed medium, and incubate for 36 h. Take the bacterial suspension and filter it with sterile gauze, and shake it with glass beads to form a single spore suspension. . Collect the single spore suspension for later use.

[0033]The spore suspension was placed under a 15 W ultraviolet lamp, with a vertical distance of 30 cm, and irradiated while stirring. Dilution coating plates were then performed under red light and cultured in the dark.

[0034] Take mutagenic bacteria with a lethality rate of 85% by ultraviolet mutagenesis, and enrich and culture them for 36 hours. Take the bacterial suspension and filter it with sterile gauze, and shake it with glass beads to break up to a single-spore suspension.

[0035] Take an appropriate a...

Embodiment 2

[0038] Production of Lovastatin by Liquid Fermentation of Monascus

[0039] Fermentation strain: Monascus purpureus

[0040] Seed Medium:

[0041] Rice flour 3 g, glucose 2 g, NaNO 3 0.2 g, peptone 1.5 g, MgSO 4 ·7H 2 O 0.05 g, KH 2 PO 4 0.15 g, add water to 100 mL.

[0042] Fermentation medium:

[0043] Rice flour 7 g, glycerin 5 mL, NaNO 3 0.2 g, peptone 1.5 g, MgSO 4 ·7H 2 O 0.05 g, KH 2 PO 4 0.15 g, add water to 100 mL.

[0044] Training conditions:

[0045] Monascus spores were scraped from the plate and transferred to a Erlenmeyer flask containing 50 mL of seed medium, and cultured at 30°C for 3 days. According to the inoculation amount of 15%, the grown seed culture medium was transferred to 150 mL fermentation medium, cultured on a shaker at 150 r / m at 30°C for 3 days, and then cultured on a shaker at 150 r / m at 30°C for 14 days.

[0046] Sample processing and testing:

[0047] After the fermentation broth was centrifuged at 10,000 g for 10 min, 2...

Embodiment 3

[0050] Production of lovastatin by liquid fermentation of Monascus after mutagenesis

[0051] Fermentation strain: Monascus MPB2

[0052] Seed medium:

[0053] Rice flour 3 g, glucose 2 g, NaNO 3 0.2 g, peptone 1.5 g, MgSO 4 ·7H 2 O 0.05 g, KH 2 PO 4 0.15 g, add water to 100 mL.

[0054] Fermentation medium:

[0055] Rice flour 7 g, glycerin 5 mL, NaNO 3 0.2 g, peptone 1.5 g, MgSO 4 ·7H 2 O 0.05 g, KH 2 PO 4 0.15 g, add water to 100 mL.

[0056] Training conditions:

[0057] The spores of Monascus MPB2 were scraped from the plate and transferred to a Erlenmeyer flask containing 50 mL of seed medium, and cultured at 30°C for 3 days. According to the inoculation amount of 15%, the grown seed culture medium was transferred to 150 mL fermentation medium, and cultured on a shaker at 150 r / m at 30°C for 3 days, then cultured on a shaker at 150 r / m at 24°C for 20 days.

[0058] Sample processing and testing:

[0059] After the fermentation broth was centrifuged ...

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Abstract

The invention belongs to the field of microbial technologies, and particularly relates to a production method of high-ring-opening-rate lovastatin. The method comprises the steps of mutagenizing monascus purpureus and fermenting the mutagenized strain. The method has the beneficial effects that according to the mutagenized strain and lovastatin production method disclosed by the invention, compared with conventional monascus production strains and production methods thereof, the ring opening rate of obtained lovastatin can be increased by over 1.5 times, and reach 68.9%, so that lovastatin products with higher quality are obtained.

Description

technical field [0001] The invention belongs to the technical field of microorganisms, and in particular relates to a production method of lovastatin with a high ring-opening rate. Background technique [0002] Lovastatin is a physiologically active substance that can inhibit the synthesis of cholesterol in the body. Since 1987, the American Merck Company developed the lovastatin series and launched a new generation of cholesterol-lowering drugs. Patients welcome. [0003] Lovastatin generally exists in two forms: open ring and closed ring. Under acidic conditions, the ring-opening form is the main form, and there is a small amount of closed-ring form. Under certain conditions, the two forms can be converted into each other. Currently on the market, the main component of pharmaceutical lovastatin lipid-lowering drugs is closed-loop lovastatin. Closed-loop lovastatin itself has no lipid-lowering activity and needs to be hydrolyzed by hydroxyl esterase in the human body, th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/01C12N13/00C12P17/06C12R1/645
Inventor 陈泉李纪顺赵吉兴李耀杨合同吴远征扈进冬王贻莲闫芃韩岩君
Owner 山东中惠生物科技股份有限公司
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