The cyclic undecapeptide,cyclosporin A (CyA),is one of the most commonly-prescribed immunosuppressive drugs.It is generated non-ribosomally from a multi-functional cyclosporin synthetase enzyme complex by the filamentous fungus,Tolypocladium niveum.The various structural modifications of cyclosporins such as a regiospecific hydroxylation at N-methyl leucines lead to a dramatic changes of their bioactive spectra.