Fermentation Optimization Of Nucleoside Antibiotic Capuramycin And Albomycin

Objectives 1 To optimize the fermentation conditions of Capuramycin and find the optimal concentration of each component of the fermentation condition. By studying the time and feeding concentration of threonine in fermentation process. Based on the above optimum conditions,we can get the optimum fermentation conditions of Capuramycin.2 To learn the activity of Capuramycin in the bacteriostatic experiment and the Murine Model of Tuberculosis,providing references for further study.3 Trying to get the best combination of Albomycin fermentation conditions,and study the impact of the final yield of Albomycin when we supplemented with ferrous sulfate in fermentation process. By optimizing the two nucleoside antibiotic fermentation conditions to achieve the need for further research,and privide a theoretical basis for the large-scale fermentation.Methods 1 The main factors that determine the effects of single factor experiment fermentation yield, Plackett-Burman design was designed two experiments to determine the level of the major factors from the significant factor.Steepest ascent experiment to determine the optimal concentration range of each major factor in the significant factor based on the experimental results obtained Plackett-Burman designs, the results obtained using response surface methodology for final optimization of fermentation conditions to obtain the optimal combination. After the fermentation period, the use of two antibiotics are fed to improve the final yield.2 To evaluate the antibacterial activity of Capuramycin by the experiment in vitro and in vivo.Results The single factor designs we were used to found the best lever of single factor in fermentation factors,so we can found that the main factors from the single factor design:starch12.1g/L,glucose22.7g/L,Na Cl1.2g/L,(NH4)SO42.3g/L,Mg SO41.3g/L,Ca CO34g/L,a single culture condition:inoculation amount of 10%,temperature 29 o C,ration speed220r/min,the cultivate time of seed culture is 2days,the fermentation time is8 days.Albomycin fermentation conditions in determining glucose as the carbon source,yeast extract as the nitrogen source.Plackett-Burman designs were used to determine the factors on the fermentation medium of Albomycin.We found major factors is glucose,Fe SO4 and ration speed.To determine the best combination of range to fermentation conditions of Capuramycin and Albomycin.The optimal combined conditions were further optimized by response surface methodology.We used the followed condition and get the result of Capuramycin shows that the production could reachedto13.61mg/L,starch12.1g/L,glucose22.7g/L,Na Cl1g/L,(NH4)SO42.3g/L,Mg SO41g/L,Ca CO31g/L;temperature29?ration speed224r/min,the cultivate time of seed culture is2 days, the fermentation time is 8 days. The threonine fed to the fermentation medium was 200mg/L by120 h.The production of Capuramycin was improved 23.15% compared that of previous.The result of Albomycin shows that the production could reached up to11.47mg/L by the followed condition:glucose 13.1g/L,yeast extract 20g/L,KH2PO4 42g/L,(NH4)SO22g/L,Fe SO42.6g/L,ration speed224r/min,temperature29?inoculum size of 10%.Feeding ferrous sulfate concentration of 1g/L, p H was adjusted to 6.5.The production of Albomycin was improved 26.45% compared that of previous.2 The antibacterial activity of Capuramycin against MDR-TB were significantly better than Isoniazid and Rifampicin.We also prove that the liver toxicity of Capuramycin is less than Isoniazid and Rifampicin.Conclusions Results of the production to the two Nucleoside antibiotic of Capura mycin and Albomycin by Response Surface methodology has been improved comp ared to previous production while in the middle of fermentation feeding also helps to improve the yield of two antibiotics.In accordance for the following experimen tal study.The results of experiment prove that Capuramycin have great prospect to anti-TB drug.