Effect of Amino Acids and Organic Nitrogen Sources on Cyclosporin A Fermentation by Tolypocladium inflatum

Cyclosporin, an immunosuppressant, is a representative group of biologically active secondary metabolites produced by the fungus Tolypocladium inflatum. The amount and ratio of cyclosporin derivatives in the culture broth are an important factors for the production of cyclosporin A and the purification in the industrial process. Therefore, we studied the effect of amino acids and complex organic nitrogen sources using Tolypocladium inflatum mutants on the productivity of cyclosporin A and the ratio of cyclosporin derivatives. Overproducing mutant YHC-004 having seven times higher productivity than mother strain's could be obtained through the artificial mutation by UV irradiation. The concentration and kind of organic nitrogens and amino acids shows the profound effect on the productivity of cyclosporin A and ratio of cyclosporin derivatives. As a result, it was possible to raise the productivity and the ratio of cyclosporin A up to 3,430 mg/L and 93% respectively, but on the other hand the other cyclosporin derivatives decreased less than 2% in the culture broth.