UK-2A, B, C and D, novel antifungal antibiotics from Streptomyces sp 517-02 V. Inhibition mechanism of bovine heart mitochondrial cytochrome bc(1) bythe novel antibiotic UK-2A

UK-ZA is a potent antifungal antibiotic isolated from Streptomyces sp. 517- 02 and its structure is highly similar to that of antimycin A. We investiga ted the inhibition mechanism of bovine heart mitochondrial cytochrome bc(1) complex by the UK-2A using antimycin A and myxothiazol as the reference in hibitors of ubiquinol oxidation (Q(o)) and ubiquinone reduction (Q(i)) site s, respectively. The inhibitory potency of UK-ZA was about 3-fold less than antimycin A. On the basis of the effects of UK-2A on the reduction kinetic s of b and c(1) hemes, this compound appeared to be an inhibitor of the Q(i ) site. However, since spectral changes of dithionite-reduced cytochrome b induced by UK-2A binding differed from that of antimycin A, the precise bin ding manner of UK-2A to the enzyme is not identical to that of antimycin A. It could be concluded that antimycin A binding to cytochrome b is primaril y decided by structural specificity of the salicylic acid moiety.