Tolypocladium niveum

Weber, G., Schorgendorfer, K., Schneider-Scherzer, E. and Leitner, E. (1994) The peptide synthetase catalyzing cyclosporine production in Tolypocladium niveum is encoded by a giant 45.8-kilobase open reading frame. Current Genetics, 26 (2), 120-125. 

Cyclosporins, produced by the filamentous fungus Tolypocladium niveum and by numerous strains of Fusaria and Neocosmospora, are a class of cyclic undecapep-tides which are composed of hydrophobic aliphatic amino acids [73-75], They exhibit antiinflammatory, immunosuppressive, antifungal, and antiparasitic properties [74], The main metabolite, cyclosporin A, is in clinical use worldwide under the trade name SANDIMMUN to prevent allograft rejection [77,78], Besides cyclosporin A, there are 24 naturally occuring cyclosporins which have substitutions of amino acids in positions 1, 2, 4, 5, 7, and 11 and/or contain unmethylated peptide bonds in positions 1,4,6,9,10, or 11 [79-82], Cyclosporin A contains three nonproteinogenic amino acids D-alanine in position 8, L-a-aminobutyric acid in position 2, and, in position 1, the unusual amino acid 4(R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (Bmt) (Fig. 8). All three amino acids have to be synthesized by a pathway independent of the primary metabolism. In addition, several peptide bonds of the cyclosporin molecule are A -mcthylated similar to the depsipeptides enniatin, beauvericin and PF1022A-related peptides. 

G Weber, E Leitner. Disruption of the cyclosporin synthetase gene of Tolypocladium niveum. Curr Genet 26 461-467, 1994. 

Efrapeptins such as efrapeptin D (24 in Figure 5) were isolated from the entomopathogenic fungus Tolypocladium niveum. They have a unique linear peptide structure with a bicyclic amine moiety at their C-terminus and show insect toxicity by inhibiting mitochondrial ATPase.7... 

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... 

Gupta, S., Krasnoff, S.B., Roberts, D.W. et al (1991) Structures of tbe efrapeptins Potent inhibitors of mitochondrial ATPase from the fungus Tolypocladium niveum. Journal of the American Chemical Society, 113, 707-709. 

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