INDUCTION OF CEPHALOSPORIN C IN Cephalosporium acremonium USING U.V. LIGHT AND SELECTION OF A MUTANT THAT SHOWED HIGHEST FERMENTATION CAPABILITY

Ultraviolet-light mutagenesis had been used in the induction of cephalosporin C (CPC) production in Cephalosporium acremonium ATCC 11550. Selection of high antibiotic-producers among the mutants was carried out by agar diffusion method using Bacillus subtilis ATCC 6633, and then final selection of the highest CPC producing mutant was carried out in shake flasks in which it produced 900 mg/L. The newly-isolated mutant (M104) produced 2160 mg/L CPC in a batch process in NBS stirred-tank bioreactor (working volume 4L). The fermentation and sugar assimilation behavior of the strain M104 have been investigated. It has been observed that adequate aeration is critically important to supply oxygen that is necessary for antibiotic biosynthesis. The diauxic phenomenon has been observed in this fermentation process in which a mixture of an easily metabolized sugar (glucose) with another more difficult to be assimilated (sucrose) is used to build up the antibiotic-producing biomass (by glucose) and to make the fungus attain the physiological state of antibiotic production (by sucrose). The maximum CPC concentration was obtained at 96 hours of fermentation time, the maximum specific productivity was 186 mg CPC/g dry weight at 136 hours, and the maximum rate of CPC production was 31 mg/L.hr at 64 hours. This work is considered a model of strain genetic improvement that is carried out to enhance the antibiotic production in industry to increase the profit with a reduction of the cost of the final product.