The Mode of Action of UK-2A and UK-3A, Novel Antifungal Antibiotics from Streptomyces sp. 517-02.

The Journal of Antibiotics
1997.0

Abstract

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 β-hydroxybutyrate and succinate as a respiratory substrate, but no inhibition was observed using ascorbate-reduced tetramethyl β-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. UK-2A~D and UK-3A were isolated as antifungal antibiotics from the acetone extracts of mycelia of Streptomyces sp. 517-02. UK-2A-D and UK-3A were very similar in structure to antimycin antibiotics. The former's activity was as strong as that of antimycin A, while that of the latter was not so potent. Interestingly, UK-2A~D and UK-3A demonstrated very weak cytotoxicity compared to antimycin A. Antimycins are well-known not only as antibiotics but also as insecticides, miticides, etc. They are used as specific mitochondrial respiratory chain inhibitors only in laboratory studies because of their broad toxicity. This paper describes the mode of action of UK-2A and UK-3A compared with that of antimycin A3.

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