Traminines A and B, produced by Fusarium concentricum, inhibit oxidative phosphorylation in Saccharomyces cerevisiae mitochondria. (3rd August 2021)

• Record Type: Journal Article
• Authors: Sakai, Katsuyuki; Unten, Yufu; Kimishima, Aoi; Nonaka, Kenichi; Chinen, Takumi; Sakai, Kazunari; Usui, Takeo; Shiomi, Kazuro; Iwatsuki, Masato; Murai, Masatoshi; Miyoshi, Hideto; Asami, Yukihiro; Ōmura, Satoshi
• Is Part Of: Journal of industrial microbiology & biotechnology. Volume 48:Number 9/10(2021)
• Publication Date: 2021-08-03
• Subjects: Saccharomyces cerevisiae -- Multidrug-sensitive -- Mitochondria; Industrial microbiology -- Periodicals; 660.62
• DOI: 10.1093/jimb/kuab051
• Languages: English
• ISSNs: 1367-5435

Abstract

Abstract: Two new tetramic acid derivatives, traminines A (1 ) and B (2 ), were isolated from a culture broth of Fusarium concentricum FKI-7550 by bioassay-guided fractionation using multidrug-sensitive Saccharomyces cerevisiae 12geneΔ0HSR-iERG6. The chemical structures of 1 and 2 were elucidated by NMR studies. Compounds 1 and 2 inhibited the growth of the multidrug-sensitive yeast strain on nonfermentable medium containing glycerol, but not on fermentable medium containing glucose. These results strongly suggest that they target mitochondrial machineries presiding over ATP production via oxidative phosphorylation. Throughout the assay monitoring overall ADP-uptake/ATP-release in yeast mitochondria, 1 and 2 were shown to inhibit one or more enzymes involving oxidative phosphorylation. Based on biochemical characterization, we found that the interference with oxidative phosphorylation by 1 is attributable to the dual inhibition of complex III and Fo F1 -ATPase, whereas that by 2 is solely due to the inhibition of complex III.