INFLUENCE OF AMINO-ACIDS ON THE BIOSYNTHESIS OF CYCLOSPORINE-A BY TOLYPOCLADIUM-INFLATUM

An indigenously isolated strain of Tolypocladium inflatum, when grown as a suspension culture in semi-synthetic and synthetic media, produce d cyclosporin A. Biosynthesis of this well-known immunosuppressive age nt was found to be influenced heavily by the external addition of the amino acid constituents of the molecule. In synthetic media, L-leucine and L-valine were found to act as strong inducers of drug production. L-Valine increased the specific production of cyclosporin A by 75% in semi-synthetic medium and by ten times in synthetic medium compared t o an unsupplemented control culture. D-Valine had no stimulating effec t on the production. The presence of amino acids in the exponential gr owth phase ensured optimal production, as was indicated in the experim ent in which L-valine was added at different times: 4 g/l was the opti mum concentration of exogenous L-valine. On the other hand, exogenous sarcosine and L-methionine tended to diminish drug production.