Study On The Breeding And Fermentation Technology Of High-yielding Cephalosporin C-producing Cephalosporium Acremonium Strains

Cephalosporin antibiotics have good curative effect,low toxicity,hypoxylase resistance,low allergic reaction and wide antimicrobial spectrum.At present,more than 60 cephalosporin antibiotics have been used,which accounted for more than 50%of the total amount of antibiotics.China is the world's leading producer of cephalosporin raw materials,and the competition among domestic and foreign manufacturers isfierce.As the cost of the raw materialsof cephalosporin C keeps increasing,and the state strictly restricts the use of antibiotics in clinical practice,a better strains and optimize manufacturing technique for cephalosporin C production is urgently needed by the enterprise.The present study take the cephalosporus that used to produce cephalosporin C as the research object,and the rational selectionwas used to screen the high-yielding strain.In addition,the fermentation medium and thefermentation processforce phalosporin C productionwere studied to improve the fermentation unit of cephalosporin C and reduce the cost of cephalosporin Cproduction.The main research results are as follows:Using HX-5 as the initial strain to carry out rational selection of cephalosporins,and the screening concentration of cupric ion,malonic acid and cephalosporin C sodium salt were determined in the present study.Finally,the high-yielding strains ht-103,hb-085 and hc-008were screened.The potency was increased by 11.2%,6.0%and 20.8%,respectively,as compared tothe original initial strain.The optimal concentration of fermentation medium was determined by optimizing the fermentation medium,which was 60 g·L^-1for soybean oil,60 g·L^-1for corn pulp,6 g·L^-1for methionine,7 g·L^-1for KH₂PO₄,0.3 g·L^-1for Fe²⁺,0.02 g·L^-1for Zn SO₄,0.01 g·L^-1for Mn SO₄,and 0.02 g·L^-1for Cu SO₄.Soybean oil was replaced by 50%methyl oleate,and 10g·L^-1corn pulp was replaced by 5 g·L^-1soybean meal powder.The yield of cephalosporin C was higher.The fermentation process was improved,in whichthe p H value before sterilization was determined to be within the range of 7.2-7.6.The optimal loading amount was 2.6 L,the inoculation amount was 20%,and the optimal temperature change time were 40 h.The Do-stat supplementation was carried out with the combination of glucose and soybean oil,and the yield of cephalosporin C were significantly increased.The optimized titer of cephalosporin C increased by about 10%.