The mode of action of UK-2A and UK-3A, novel antifungal antibiotics from Streptomyces sp. 517-02.

UK-2A and UK-3A are structural relatives of antimycins, which were isolated as antifungal antibiotics with little cytotoxicity that demonstrated inhibition of respiratory activity. They halve the cellular respiration of yeast within 4-5 minutes and the intracellular ATP content within 2-5 minutes. Moreover, they inhibited the yeast mitochondrial respiration using beta-hydroxybutyrate and succinate as a respiratory substrate, but no inhibition was observed using ascorbate-reduced tetramethyl p-phenylenediamine as the substrate. The site of respiratory inhibition of UK-2A and UK-3A was thought to be the cytochrome bc1 complex in the mitochondrial electron transport chain of yeast cells. They also inhibited the mitochondrial respiration of rat liver. It has been suggested that intact animal cells might have some system to defend themselves from the actions of UK-2A and UK-3A.