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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Growth inhibition dependent on reactive oxygen species generated by C9-UK-2A, a derivative of the antifungal antibiotic UK-2A, in Saccharomyces cerevisae
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Growth inhibition dependent on reactive oxygen species generated by C9-UK-2A, a derivative of the antifungal antibiotic UK-2A, in Saccharomyces cerevisae

机译：在酿酒酵母中，生长抑制取决于C9-UK-2A（抗真菌抗生素UK-2A的衍生物）产生的活性氧种类

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摘要

UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A(3) (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. C9-UK-2A, which has been prepared to improve the duration of the antifungal activity of UK-2A, shows durable fungicidal activities against various species of fungi and induces both membrane injury and the generation of cellular reactive oxygen species (ROS) against Rhodotorula mucilaginosa IFO 0001 cells. We found that C9-UK-2A inhibited the vegetative growth of Saccharomyces cerevisiae IFO 0203 cells accompanying cellular ROS generation in Sabouraud dextrose (SD) medium, which contained a fermentable carbon source. The ROS generation was completely restricted by pretreatment with a lipophilic antioxidant alpha-tocopherol. In addition, the pretreatment with the antioxidant protected against the growth inhibition induced by C9-UK-2A. C9-UK-2A also induced ROS generation in isolated mitochondria of the S. cerevisiae cells. The addition of both a complex I inhibitor rotenone and a complex II inhibitor thenoyltrifluoroacetone reduced ROS generation induced by C9-UK-2A in the whole cells and the isolated mitochondria. The addition of the inhibitors of complex III, AA or myxothiazol, or of complex IV, KCN, did not reduce ROS generation. These results suggest that C9-UK-2A induces ROS generation due to the blockade of electron flow at complex III, thereby inhibiting the growth of S. cerevisiae in SD medium.
机译：UK-2A是一种有效的抗真菌抗生素，其结构与抗霉素A（3）（AA）高度相似。 UK-2A和AA抑制复合物III处的线粒体电子传输。 C9-UK-2A的制备旨在提高UK-2A的抗真菌活性的持续时间，它显示出对各种真菌的持久杀真菌活性，并诱导膜损伤和针对红球菌的细胞活性氧（ROS）生成粘菌IFO 0001细胞。我们发现C9-UK-2A抑制了酿酒酵母IFO 0203细胞的营养生长，并伴随着在含有可发酵碳源的萨氏葡萄糖（SD）培养基中细胞ROS的生成。通过用亲脂性抗氧化剂α-生育酚预处理完全限制了ROS的产生。此外，用抗氧化剂进行的预处理可防止C9-UK-2A诱导的生长抑制。 C9-UK-2A还可以在酿酒酵母细胞的分离的线粒体中诱导ROS的产生。复杂的I抑制剂鱼藤酮和复杂的II抑制剂壬基三氟丙酮的加入减少了C9-UK-2A在整个细胞和分离的线粒体中诱导的ROS生成。添加复合物III（AA）或甲噻唑或复合物IV（KCN）的抑制剂不会减少ROS的产生。这些结果表明，C9-UK-2A由于络合物III处的电子流受阻而诱导了ROS的产生，从而抑制了酿酒酵母在SD培养基中的生长。

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