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Traminines A and B, produced by Fusarium concentricum, inhibit oxidative phosphorylation in Saccharomyces cerevisiae mitochondria
Journal of Industrial Microbiology & Biotechnology ( IF 3.2 ) Pub Date : 2021-07-31 , DOI: 10.1093/jimb/kuab051
Katsuyuki Sakai 1 , Yufu Unten 2 , Aoi Kimishima 1, 3 , Kenichi Nonaka 1, 3 , Takumi Chinen 4 , Kazunari Sakai 1, 3 , Takeo Usui 4 , Kazuro Shiomi 1, 3 , Masato Iwatsuki 1, 3 , Masatoshi Murai 2 , Hideto Miyoshi 2 , Yukihiro Asami 1, 3 , Satoshi Ōmura 3
Affiliation  

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 FoF1-ATPase, whereas that by 2 is solely due to the inhibition of complex III.

中文翻译:

同心镰刀菌产生的 Traminine A 和 B 抑制酿酒酵母线粒体中的氧化磷酸化

使用多药敏感的酿酒酵母 12geneΔ0HSR-iERG6,通过生物测定指导的分级分离从同心镰孢 FKI-7550 的培养液中分离出两种新的曲胺酸衍生物曲胺 A (1) 和 B (2)。通过核磁共振研究阐明了1和2的化学结构。化合物 1 和 2 抑制多药敏感性酵母菌株在含有甘油的不可发酵培养基上的生长,但在含有葡萄糖的可发酵培养基上没有抑制作用。这些结果强烈表明它们针对通过氧化磷酸化主持 ATP 生产的线粒体机器。在整个监测酵母线粒体中总体 ADP 摄取/ATP 释放的测定中,显示 1 和 2 抑制一种或多种涉及氧化磷酸化的酶。根据生化特征,
更新日期:2021-07-31
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