UK-2D

Novel antifungal antibiotics, UK-2A, B and a mixture of C and D, were obtained from the mycelial cake of Streptomyces sp. 517-02. All of the UK-2 compounds were similar in structure to antimycin A. The antifungal activities of UK-2 compounds were as strong as that of antimycin A. However, the UK-2 compounds demonstrated weak cytotoxicity compared to antimycin A.

UK-2A is a potent antifungal antibiotic isolated from Streptomyces sp. 517-02 and its structure is highly similar to that of antimycin A. We investigated the inhibition mechanism of bovine heart mitochondrial cytochrome bc1 complex by the UK-2A using antimycin A and myxothiazol as the reference inhibitors of ubiquinol oxidation (Qo) and ubiquinone reduction (Qi) sites, respectively. The inhibitory potency of UK-2A was about 3-fold less than antimycin A. On the basis of the effects of UK-2A on the reduction kinetics of b and c1 hemes, this compound appeared to be an inhibitor of the Qi site. However, since spectral changes of dithionite-reduced cytochrome b induced by UK-2A binding differed from that of antimycin A, the precise binding 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 primarily decided by structural specificity of the salicylic acid moiety.

UK-2A, B, C and D, novel antibiotics produced by Streptomyces sp. 517-02, exhibit strong antifungal activity. The structures were elucidated based on spectral and chemical evidence that these compounds are the derivatives of the nine-membered dilactone formed from serine and 4-hydroxypentanoic acid moiety.