Optimization and Pilot Scale-up of Fermentation Process of Dalbavancin Precursor A-40926 B0
Objective To establish a high-yield pilot fermentation process of dalbavancin precursor A-40926 B0.Methods Nonomuraea sp.DB-3-04 was selected as the experimental strain,and the content of dalbavancin precursor A-40926 B0 in the fermentation broth was determined by HPLC.The effects of pH,fermentation temperature,dissolved oxygen,inoculation amount and feeding process on the yield of A-40926 B0 in 200 L fermenter tank were investigated.The fermentation parameters of 200 L fermenter tank were amplified to 500 L and 5000 L pilot tanks,and the step by step amplification fermentation experiments were carried out.Results The optimum fermentation conditions of 200 L test tank were as follows:the pH was maintained at about 7.5 after 72 h of incubation,the culture temperature was 28 ℃,the dissolved oxygen was not less than 50%,the inoculation amount was 9%,the stirring speed was 300 r/min,the aeration volume was 6 m3/h,and the yield of A-40926 B0 reached 3568.91 mg/L.The yield of A-40926 B0 in 500 L and 5000 L pilot tanks reached 3436.61 mg/L and 3348.25 mg/L,respectively.Conclusion The high-yield pilot fermentation process of A-40926 B0 is successfully established,which can provide reference for its industrial production.