Selection Of High Cephalosporin C Producing Cephalosporium Acremonium And Optimization Of Its Production Medium

Cephalosporin C, a member of beta-lactam antibiotic family, is produced by Cephalosporium acremonium. As it has a strong antibacterial activity against most gram-positive bacteria and gram-positive bacteria, so far thousands of Cephalosporin compound had been made by chemical modification, and tens of them have been supply of the market. It is one of the most popular antibiotics in the world.To increase the productivity of Cephalosporin C fermentation, strain breeding and fermentation optimization were perfored, and the results were as follows.Natural selection, UV mutation, and compound mutation were used to improve the production of Cephalosporin C by C. acremonium, the result showed that UV mutation is a effective method for screening high-producing strain, and that the effect of compound mutation was not as high as expected. A high Cephaloporin C producing mutant C. acremonium C32 was obtained by UV mutation and compound mutation, and its production reached 31.90g/L. Subculture tests indicated that the inherited characteristic of high Cephalosporin C productivity was stable.The Cephalosporin C fermentation in shake flasks by C. acremonium C32 was studied. The production medium and culture conditons were optimized both by ’One-Variable-at-a-Time’approach and experimental designs based on statistical methods. The optimized medium and culture conditions were as follows:peanut meal 2.98%, Tuna Soluble Extract 3.43%, corn steep liquor 1.75%, DL-Methionine 0.65%, (NH4)2SO41.06%, corn flour 1.98%, high fructose syrup 4.29%, industry wheat gluten powder 3.82%, CaSO4 1.49%, CaCO3 3.36%, inoculum level 8%, working volume ratio 10%, initial pH 7.0, culture temperature 30℃. Under the above optimized conditions, C. acremonium C32 could produce 35.946g/L Cephalosporin C after 148h cultivation of fermentation in the shake flask, which was 10.3% higher than that before optimization and is nearly consistent with the calculated one.In order to increase the efficiency of strain improvement, the multiple-tube fermentation technique for Cephalosporin C fermentation was developed, and its production medium and production condition were studied. The results showed that the multiple-tube fermentation technique can be used for screening high Cephalosporin C producing Cephalosporium acremonium.