ENHANCEMENT OF CYCLOSPORINE PRODUCTION IN A TOLYPOCLADIUM-INFLATUM STRAIN AFTER EPICHLOROHYDRIN TREATMENT

Following treatment of conidia of the cyclosporin producer fungus, Tolypocladium inflatum. with 0.15 M epichlorohydrin, strain M6 was isolated. The new strain exhibited a similar growth rate to the parent organism but more extensive conidiation and several-fold higher overall cyclosporin production. Strain M6 reached titres of 318 mg 1-1 cyclosporin A in agar cultures, whereas in liquid medium it produced 140 mg 1-1 cyclosporin A and 68 mg 1-1 cyclosporin C. It also maintained a steady volumetric productivity of 0.48 mg 1-1 h-1 cyclosporin A over 2 weeks of submerged cultivation in maltose-based semisynthetic medium. The new strain holds potential for improved cyclosporin production due to the superior titres and demonstrated capacity to sustain elevated production of cyclosporin for periods greater than the wild type. © 1990.