Cyclosporin-A production by Tolypocladium inflatum using solid state fermentation

Tolypocladium inflatum strains are known to produce Cyclosporin-A under submerged culture conditions. In the present study solid state fermentation was used to produce Cyclosporin-A. Tolypocladium inflatum strains when grown on moist wheat bran produced 310-459 mg of Cyclosporin-A kg of bran(-1). Tolypocladium inflatum ATCC 34921 which produced 459 mg of Cyclosporin-A. kg of bran(-1) was improved to produce 1031 +/- 27 mg of Cyclosporin-A kg(-1) of bran, by subjecting the spores to different mutagenic treatments. The mutated strain, designated Talypocladium inflatum DRCC 106, produced 4843 mg kg(-1) of bran under optimum fermentation conditions in 10 days when grown on wheat bran medium containing millet flour 20%, jowar flour 10%, zinc sulphate 0.15%, ferric chloride 0.25% and cobaltous chloride 0.05%. An inoculum of 60% initial moisture content 70%, initial bran pH 2.0 and incubation temperature 25 degrees C were found to be optimal. Cyclosporin-A thus obtained was purified by solvent extraction, followed by column chromatography. The isolated product complies with the United States Pharmacopoeia. specifications. (C) 1999 Elsevier Science Ltd. All rights reserved.