The biochemistry of cyclosporin formation: a review

Abstract

The cyclosporins are a group of over 25 closely related cyclic undercapeptides produced as secondary fungal metabolites by Cylindrocarpum lucidum Booth and Tolypocladium inflatum Gams. Both strains of fungi imperfecti were isolated from soil samples collected in Wisconsin (USA) and Hardanger Vidda (Norway). The isolation, the culture conditions and the taxonomy of these fungi are reported by Dreyfuss et al. 1 Cyclosporin (CS), originally named ‘Cyclosporin A’, is the main component of this family of cyclic peptides each comprising 11 amino acids. The producing strain (NRRL 8044) was initially misidentified as Trichoderma polysporum 2 but is now initially referred to as Tolypocladium niveum. 3 T. niveum has also been classified as Tolypocladium inflatum 4 and as Beauveria nivea. 5 The production of CS by some strains of the phytopathogenic fungus Neocosmospora spp. was described by Dreyfuss. 6 CS was isolated initially for its antifungal activities. Extracts of cultures exhibit in vitro a narrow spectrum of anti-fungal activities but exert only marginal effects in vivo. Borel et al. 7–9 also reported CS activity as an immunosuppressant which acted mainly on Tlymphocytes, showed anti-infammatory effects and was practically devoid of toxicity. It is unique among the presently available immunosuppressive drugs in that it reversibly inhibits only some classes of lymphocytes and does not affect haemopoietic tissues (bone marrow).