Streptomycete and use thereof in tacrolimus production by multi-stage fermentation

Abstract

The invention discloses a streptomyces and application of the streptomyces in a multistage tacrolimus fermenting production method, and further provides the multistage tacrolimus fermenting production method that utilizes the streptomyces sp., which comprises the steps of seed cultivation, inoculation preparation, inoculation, multistage dissolved oxygen control, batch-fed fermentation, and multistage fermenting production of the streptomyces sp.NJYH2618, thus remarkably raising the yield of tacrolimus that is a secondary metabolite of the streptomyces sp. The invention has low cost, simple operation and higher potency of the tacrolimus that is a target product in a fermented liquid, and is favorable for industrial scaled production.

Description

technical field The invention belongs to the technical field of fermentation engineering, and in particular relates to a multi-stage fermentation production method of Streptomyces sp., a high-yield macrolide immunosuppressant tacrolimus. Background technique Tacrolimus (tacrolimus, FK506) is an important macrolide immune agent, which was first discovered by Fujisawa Pharmaceutical in Japan in 1984. It has been widely used in liver, bone marrow transplantation, and kidney transplantation resistant to other drugs. Prevention and treatment of rejection, Behcet's disease, allergic dermatitis, psoriasis, ichthyosis, alopecia areata, rheumatoid arthritis, psoriasis, multiple sclerosis, diabetes and other autoimmune diseases. Since its launch in China within a short period of time, its market share has risen rapidly, and it has become a clinical first-line drug for rejection after liver and kidney transplantation. However, most of the domestic market is currently occupied by countr...

AI Technical Summary

Problems solved by technology

In view of the problems of long fermentation period, many intermediate products, long extraction and separation steps, and high-concentration product substrate inhibition in the current production of tacrolimus by fermentation methods at home and abroad, if a systemic fermentation method can be established to produce tacrolimus The basic theory of multi-stage reaction and separation coupling, especially the in-depth research on the separation, extraction and transformation of products, provides templates for the biological production of antibiotics and other secondary metabolites, which is of great significance for further consolidating the platform for biological synthesis of antibiotics

Images