Process for fermenting rapamycin with high yield

Abstract

The invention provides a process for fermenting rapamycin with high yield, and belongs to a method for preparing antibiotics by utilizing fermentation of microorganism in the technical field of biology. According to the method, enzymolytic cotton seed powder, dextrin, glycerinum, yeast extract, L-lysine, KH2PO4, K2HPO4, (NH4)2SO4 and trace elements as culture media, wherein the trace elements contain Co<2+>, glycerinum and phosphate buffer are fed in the early phase of the fermenting culture process, and L-pipecolic acid and shikimic acid are fed in the synthesizing phase. By adopting the method, the methyl derivative can be reduced in the growing phase, and the content of rapamycin is increased; intermediate products can be reduced, and rapamycin can generate key enzyme activity; the beneficial effect of high yield of rapamycin can be achieved.

Description

technical field [0001] The invention belongs to a method for producing antibiotics by microbial fermentation in the field of biotechnology, in particular to a high-yield rapamycin fermentation process. Background technique [0002] Rapamycin (Rapamycin, RAPA), also known as Sirolimus (Sirolimus), molecular structure such as figure 1 The molecular formula of RAPA is C 51 h 79 NO 13 , molecular weight 99lKD, white solid crystal, melting point 183-185 ℃, specific rotation [ɑ] 25 D =153 0 (Methanol), lipophilic, soluble in methanol, ethanol, acetone, chloroform and other organic solvents, very slightly soluble in water, almost insoluble in ether, low and neutral pH in plasma, very fast degradation at 37°C, in plasma The half-life is 1~5h. Rapamycin is a new type of immunosuppressant of nitrogen-containing triene macrolide composed of 36-membered rings. It has anti-fungal, anti-proliferation and anti-tumor effects. In recent years, rapamycin has been successfully used cli...

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Problems solved by technology

[0009] From the above patent documents, it can be obtained that the fermentation unit of rapamycin reaches more than 600mg / L, but there are the following problems: the culture medium is unreasonable and the viscosity is high, resulting in low dissolved oxygen content in the large-scale fermentation process, which is not conducive to bacterial fermentation. During the fermentation process, there is no feeding, and the cell density is low; the feeding is unreasonable in the middle and late stages of fermentation, which is not conducive to the biosynthesis of rapamycin, resulting in low rapamycin content; there is no intermediate metabolites in the fermentation process To control, there are too many by-products in the middle of the fermentation process, the content of impurities is high, and the titer of rapamycin is low, resulting in high extraction costs

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