Studied On Spiramycin Fermentation Process And Ceramic Membrane Separation Technology

Spiramycin with an annual output of 450 t is an important raw material drug of Topfond pharmaceutical co.,which is mainly supplied to the company’s internal and manufacturers of Shangqiu and Shandong to produce acetyl spiramycin.Market share is more than 80%.Spiramycin and its derivatives are widely used in the medical and health care industry because of their advantages such as less side effects,low cross-drug resistance and low medication cost.The market prospect is broad.At present,there are still problems in the production of low fermentation titer and extraction yield,and product quality needs to be further improved.In this study,the effects of Zn²⁺ions addition time and concentration,inoculum volume of seed culture,and feeding mode on the biosynthesis of spiramycin were studied under shake flask fermentation and 15 L fermentor fermentation conditions.The filtration process was initially optimized using ceramic membrane filtration.This provides a reference for increasing the titer and the yield of extraction of spiramycin in industrial production.The content have carried on as follows.1,Adding Zn²⁺ions during the fermentation process of Streptomyces spiramyceticus,it increased the titer about 17%more than the control that added 0.24 g/L of Zn²⁺ions at 28 h in the process of shake flask fermentation.It was successfully demonstrated the role of Zn²⁺ions to promote spiramycin biosynthesis after amplification to 15 L fermentor.The titer of fermentation tank was 3590 U/m L,which was increased by about 20%.The detection of organic acids in the fermentation broth by HPLC showed that the Zn²⁺ions could stimulate the metabolism of the cells and improve the content of acetic acid and propionic acid,and further promote the spiramycin biosynthesis.2,The spiramycin titer reached 3760 U/m L at the inoculation amount of 10%in the fermentation process of Streptomyces spiramyceticus with 15 L fermentor,which increased by4.94%than the inoculation amount of 6%.Feeding methods affect the titer of spiramycin.The titer of continuous feeding fermentation tank was 3836 U/m L,which was increased by about2.1%compared with that of fed-batch fermentation tank.The rate methods of continuous feeding were adopted earlier and later lower,medium-term higher.In this way,the titer increased obviously.The titer of fermentation tank was 3946 U/m L,which was increased by about 5.03%compared with that of fed-batch fermentation tank.It was successfully demonstrated the role of continuous feeding to promote spiramycin biosynthesis after amplification to 3.8 m³ fermentor.The titer of fermentation tank reached 3943 U/m L,which was 9.71%higher than that of the fed-batch fermentation tank.3,An optimized filtration process was obtained by filtering the spiramycin fermentation broth with a ceramic membrane.Under the conditions of a ceramic membrane pore size of 50nm,a membrane pressure differential of 0.15 MPa,a temperature of 35℃and a dilution factor of 1.0,the average membrane flux was 132 L/（m²·h）,The filtrate was clear and transparent with high quality.The yield of extraction of spiramycin was 96.98%.These findings will provide useful references for improving the industrial production efficiency of spiramycin.