Trichoderma polysporum Cyclosporins

Cyclosporine is a cyclic polypeptide with potent, partially selective immuno-supressive activity. Isolated from the species Cylindrocarpon lucidium and Trichoderma polysporum, cyclosporine is useful in the prevention cmd treatment of graft/host disease and the prevention of rejection following organ transplantation. It appears to act by preferentially suppressing T-lymphocytes. Cyclosporine lacks myelotoxicity, although impaired renal 2Uid liver fimction have been observed. Initial administration is via the intravenous route, followed by oral maintenance therapy. 

The immunomodulator cyclosporin was originally isolated from a soil fungus, Trichoderma polysporum (see Chapter 40). This compound was a major breakthrough for organ transplantation, because it suppressed immunological rejection of the transplanted organ. Tacrolimus (FK-506), a secondary metabolite of Streptomyces tsukabaensis, was approved in 1994 for use as an immunosuppressant in organ transplantation (De Smet, 1997). 

M Dreyfuss, E Harri, H Hoffmann, H Kobel, W Pache, H Tscherter. Cyclosporin A and C, new metabolites from Trichoderma polysporum. Eur J Appl Microbiol 3 125-133, 1976. 

Ruegger, A., Kuhn, M., Lichti, H., Loosli, H., Huguenin, R. et al. (1976). Cyclosporin-A, a peptide metabolite from Trichoderma polysporum rifai, with a remarkable immunosuppressive activity. Helv. Chim. Acta 59, 1075-1092. 

Cyclosporine, proprietary names Sandimmune (cyclosporine) and Neoral, is a cyclic peptide composed of 11 amino acids, some of novel structure, isolated from the fungus Trichoderma polysporum (Figure 33-13). The compound has been shown effective in suppressing acute rejection in recipients of allograft organ transplants. Cyclosporine is approved for use in renal, cardiac, hepatic, pancreatic, and bone marrow transplants. 

Ruegger A, Kuhn K, Lichti H, Loosli HR, Huguenin R, Quiquerez C, von Wartburg A. Cyclosporin A a peptide metabolite from Trichoderma polysporum (Link ex Pers.) Rifai, with a remarkable immunosuppressive activity. Helv Chim Acta 59(4) 1075-1092, 1976. 

The soilborne fungus Tolypocladium niveum, originally classified as Trichoderma polysporum and then Tolypocladium inflatum, was shown to produce antifungal metabolites with a narrow antifungal spectrum [178]. The metabolites, now collectively known as the cyclosporins [179], subsequently became better known because of their potent... 

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