Culture medium for producing lipstatin and use method of culture medium

Abstract

The invention provides a culture medium for producing lipstatin. The culture medium is a combined culture medium comprising a solid screening culture medium, a slant solid culture medium, a seed solution culture medium and a fermentation culture medium. The solid screening culture medium and the slant solid culture medium both contain caprylyl-coenzyme and leucine; and the fermentation culture medium comprises a fermentation basal culture medium and a fermentation fed-batch culture medium. The idea that people depend on experience more than theory for a long time is broken through; a reactionmechanism is carefully researched and analyzed; and the mode of combining the solid screening culture medium, the slant solid culture medium, the seed solution culture medium and the fermentation culture medium is adopted, so that the certainty of the lipstatin culture process is improved, the process is more targeted, the fermentation titer of the lipstatin is obviously improved, and the averagefermentation titer of the lipstatin can reach 12.5 g / L or above and can reach 13.3 g / L to the maximum.

Description

technical field [0001] The invention belongs to the technical field of microorganisms, and in particular relates to a culture medium for producing riprestatin and a use method thereof. Background technique [0002] In 1978, Japanese scientist UmezawaH et al. isolated and extracted a potent pancreatic lipase inhibitor Esterastin from the fermentation broth of Streptomyces lavendulaeMD4-Cl, and later discovered a series of structural analogues, such as EbelactoneA and B et al. In 1987, liprestatin was obtained from the fermentation broth of S. toxytricini. Subsequently, in-depth research was carried out on its structure, physicochemical properties and drug metabolism. Roche developed its relatively stable hydrogenated product orlistat into a weight-loss drug - Xenical, which is currently the only FDA-approved target for Pancrelipase inhibitors rather than nerve center can be long-term use of weight loss drugs. It has been attracting attention because of its mild weight loss...

AI Technical Summary

Problems solved by technology

For example, U.S. patent document US2005089978A1 optimizes the fermentation process of liprestatin by adopting fed-batch feeding and intermediate feeding methods, but the fermentation level is still low, and the product titer is 1.7-1.8g / L; U.S. patent document US20110014664A1 Linoleic acid, oleic acid and γ-9 fatty acid were used to culture and ferment Streptomyces toxin to produce liprestatin, and the product titer reached 5g / L, but the fermented potency was still low, which could not meet the market demand.

[0004] In general, the low fermentation titer of liprestatin produced by biosynthesis is still the main limiting factor restricting the industrialization of orlistat