Batch type feed-batch fermentation method for streptomyces roseosporus to produce Daptomycin efficiently
2010
The invention relates to a batch type feed-batch fermentation method for streptomyces roseosporus to produce Daptomycin efficiently, comprising the following steps: taking streptomyces roseosporus slant spore at normal temperature to prepare spore suspension by sterile water; inoculating 0.5ml of the spore suspension in a 250ml shake flask filled with 30ml of seed culture medium, and culturing for 48h in a shaker when the temperature is 28-32 DEG C and the revolution speed is 180-220 rpm; adding 1% of inoculum size in an automatic 7.5 LDE fermentation tank loaded with fermentation medium; adding one or combination of cofactor ferroheme or leucovorin or pyridoxal phosphate VB6 with the concentration of 0.5-30mg/L; and controlling the throughput to be 0.8-1.2v/v/m, the pH value to be 6.5-7.5 and fermenting for 90-144h at the temperature of 28-32 DEG C. By adopting the method in the invention to regulate biological enzyme activity to increase intracellular metabolism flux introduced in Daptomycin synthesis, the Daptomycin yield is improved; the method has simple operation and low cost; and in the streptomyces roseosporus fermented and cultured by the invention, the fermentation unit of the Daptomycin can be improved by 0.24-4.6 times compared with a contrast sample.
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