Method for optimizing fermentation medium by improving rapamycin production by using metabolic profiling analysis

Abstract

The invention provides a method for optimizing a fermentation medium by improving rapamycin production by using metabolic profiling analysis, which researches dynamic changes and differences of bacteria intracellular metabolites under the culture conditions of initial fermentation medium and optimized fermentation medium by using the methods of dynamic detection and metabolic profiling analysis. The analysis result of partial least squares indicates that the bacteria primary metabolite profile and the rapamycin production have correlation and a further dynamic adding measure is provided to the medium by analyzing the dynamic changes of the key compounds combining related processes. Due to the research of S.hygroscopicus U1-6E7 fermentation medium, the rapamycin production is improved from 196mg / L to 307mg / L and is improved by 56.6%, which indicates that rational guidance of optimization of fermentation mediums by dynamic detection combining the metabolite profile analysis method is capable of successfully improving fermentation level of antibiotic and providing a new idea for optimization of fermentation mediums.

Description

technical field [0001] The invention belongs to the technical field of fermentation optimization guided by metabolic profile analysis, and particularly relates to a metabolic profile method for dynamically analyzing key metabolites affecting rapamycin synthesis in cells, and rationally guiding the addition optimization of high-yield rapamycin fermentation medium. Background technique [0002] Rapamycin is an important natural lactone compound synthesized by Streptomyces hygroscopicus, which has various biological activities, such as antifungal, immunosuppressive activity, antitumor activity, neuroprotection (Steiner et al.1997) and anti- senescence. In particular, rapamycin has potent immunosuppressive activity, which has been clinically approved for the treatment of organ transplantation anti-rejection and autoimmune diseases. In addition, semi-synthetic derivatives of rapamycin, temsirolimus and everolimus, have also been approved for clinical use in the treatment of adva...

AI Technical Summary

Problems solved by technology

However, so far, metabolic profiling has been used to dynamically detect changes in intracellular metabolites, to investigate the effects of changes in fermentation medium composition on the levels of primary metabolites and the synthesis of rapamycin in Streptomyces hygroscopicus, and to analyze the limits of rapamycin synthesis. The research on key intracellular metabolites of rapamycin, and then rationally guiding the optimization of rapamycin fermentation medium has not been reported

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