Department of Chemistry and Biochemistry, Utah State University, Logan, UT, USA.
J Antibiot (Tokyo). 2010 Nov;63(11):667-72. doi: 10.1038/ja.2010.110. Epub 2010 Oct 6.
Many Actinomycetes aminoglycosides are widely used antibiotics. Although mainly antibacterials, a few known aminoglycosides also inhibit yeasts, protozoans and important crop pathogenic fungal oomycetes. Here we show that attachment of a C8 alkyl chain to ring III of a neamine-based aminoglycoside specifically at the 4″-o position yields a broad-spectrum fungicide (FG08) without the antibacterial properties typical for aminoglycosides. Leaf infection assays and greenhouse studies show that FG08 is capable of suppressing wheat fungal infections by Fusarium graminearum-the causative agent of Fusarium head blight-at concentrations that are minimally phytotoxic. Unlike typical aminoglycoside action of ribosomal protein translation miscoding, FG08's antifungal action involves perturbation of the plasma membrane. This antibacterial to antifungal transformation could pave the way for the development of a new class of aminoglycoside-based fungicides suitable for use in crop disease applications. In addition, this strategy is an example of reviving a clinically obsolete drug by simple chemical modification to yield a new application.
许多放线菌属氨基糖苷类抗生素被广泛应用。虽然主要是抗菌药物，但少数已知的氨基糖苷类抗生素也能抑制酵母、原生动物和重要作物病原真菌卵菌。在这里，我们表明，在以小诺霉素为基础的氨基糖苷类化合物的环 III 上，在 4″-o 位接上一个 C8 烷基链，会产生一种广谱杀菌剂（FG08），而没有氨基糖苷类抗生素典型的抗菌特性。叶片感染试验和温室研究表明，FG08 能够抑制小麦真菌感染，如由镰刀菌引起的赤霉病，其浓度对植物的毒性最小。与典型的氨基糖苷类抗生素通过核糖体蛋白翻译错译的作用不同，FG08 的抗真菌作用涉及到质膜的扰动。这种从抗菌到抗真菌的转变可能为开发一类新的基于氨基糖苷类的杀菌剂铺平道路，适用于作物病害的应用。此外，这种策略是通过简单的化学修饰来恢复一种临床上已废弃药物的应用的一个例子。
