Optimization Of Cephalosporin C Fermentation Medium And Improvement Of Fermentation Process

During the Second World War, penicillin was discovered and played a significant role clinically. From then on, scientists accelerated the process of searching anti-infection drugs. In the 1950 s, people found the cephalosporin C. Due to its wide antibacterial spectrum and low toxicity, more and more cephalosporin C is applied to clinical, and the study is increasingly thorough. Our country has begun to develop varieties of cephalosporin since the 1970 s, but until now the research has been focused on the copying which is nothing different but some improvements and innovations of the technology. Up to now, there are 22 kinds of cephalosporin antibiotics preparations were applied to clinical with the approval of the state, of which only eight varieties can be produced in our country. However, the scale of production is far from satisfying the demand, and the gap between supply and demand is deep.Cephalosporin C is a kind of β-lactams antibioctis and is the raw material of Semi-synthetic cephalosporin antibiotics. 7-Aminocephalosporanic acid, the degraded product of Cephalosporin C, whose side chain can be modified and get some useful cephalosporin antibiotics. These cephalosporin drugs accounted for 30% of the global antibiotic market, and the growth of the antibiotic market in China also reached around 30%. With the rise in price of raw materials of the cephalosporin C, the control of the use of antibiotic drugs and the reform of the drug pricing system, reducing the production cost is the primary question in the production of the cephalosporin C. In industrialized production of cephalosporin C, reducing the production cost require of breeding high-yield strains, looking for a more reasonable culture medium and fermentation process.The fermentation medium and the production process of cephalosporin C were studied in this article, which is to improve the fermentation units of Acremonium chrysogenum and reduce the production cost of cephalosporin C. Optimizing nitrogen source, carbon source, and inorganic salt of fermentation medium, and on the basis of that to improve fermentation technology, especially the feeding process. As to the fermentation process of the optimized medium, we studied the adjustment of medium pH before sterilization, the capacity of fermentation tank, the feeding quantity of fermented liquid, fermentation temperature, feeding fermentation technology, the proper time to put the can respectively.First of all, in 50 L fermentor, the experimental research of culture medium and fermentation technology is to optimize the fermentation medium and improve the fermentation process. Then the experiment in 5T fermentor is to verify the result of 50 L fermentor research. The experimental research of 50 L fermentor makes the cost of fermentation medium reduce nearly 50%, and the process is simplified a lot. The feeding process, in particular, we use the soybean oil, hydrolyzed starch, corn steep liquor by 1:2:1 mixing ratio to fill material. In the past, the fermentation temperature of the fermentation technology of cephalosporin C is cooled when the time achieved 50 h, but the improved is 40 h, which save the time of heating and cooling. The former fermentation time lasts 130 hours, but now only 120 hours so the fermentation process saves the power, etc. Recently the studies of the feeding process of cephalosporin C is DO-Stat based strategy of co-feeding soybean oil and glucose, constant+DO-Stat based strategy of feeding soybean oil.The improved feeding process is the strategy of mixing of soybean oil, hydrolyzed starch, corn steep liquor by 1:2:1 ratio. Mixed feeding strategy simplifies the fermentation process, decreases the rate of bacteria infection, saves the use of soybean oil, reduces the cost of production of cephalosporin C and increases production by nearly 30%. In addition, it reduces by-products of fermentation and accords with the requirement of industrialization. The result of 5 T fermentor pilot experiments compared with the experiment in 50 L fermentor is not very ideal, but also basically achieved the result of the experiment.