Francisca Vicente , Angela Basilio , Gonzalo Platas , Javier Collado , Gerald F. Bills , Antonio González Del Val , Jesús Martín , José R. Tormo , Guy H. Harris , Deborah L. Zink , Michael Justice , Jennifer Nielsen Kahn , Fernando Peláez
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We have run an exhaustive search of sordarin-producing fungi using two different approaches consecutively, the first one being a differential sensitivity screen using a sordarin-resistant mutant yeast strain run in parallel with a wild type strain, and the second one an empiric screen against <em>Candida albicans</em><span> followed by early detection of sordarins by LC–MS analysis. Using these two strategies we have detected as many as 22 new strains producing a number of different sordarin analogues, either known (sordarin, xylarin, zofimarin) or novel (isozofimarin and 4′-O-demethyl sordarin). Sordarin and xylarin were the most frequently found compounds in the class. The producing strains were subjected to sequencing of the ITS region to determine their phylogenetic affinities. 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引用次数: 51
摘要
Sordarins是一类天然抗真菌药物,通过与延伸因子2 (EF2)的相互作用特异性抑制真菌蛋白的合成。文献报道了许多由不同种类的真菌产生的天然丹青素。我们连续使用两种不同的方法对产生sordarin的真菌进行了彻底的搜索,第一种方法是使用sordarin抗性突变酵母菌株与野生型菌株并行进行差异敏感性筛选,第二种方法是对白色念珠菌进行经验筛选,然后通过LC-MS分析早期检测sordarin。使用这两种策略,我们已经检测到多达22种新的菌株产生许多不同的sordarin类似物,无论是已知的(sordarin, xylarin, zofimarin)还是新的(isozofimarin和4 ' - o -去甲基sordarin)。Sordarin和xylarin是该类中最常见的化合物。对生产菌株进行ITS区域测序,以确定其系统发育亲和性。所有菌株均属于木木科,分布于木木科、双木科和双木科3个科。尽管进行了大量筛选,但我们没有在任何其他真菌类群中发现Sordariales, Eurotiales和Microascales等已知存在产生Sordariales真菌的目(即Sordariales, Eurotiales和Microascales)产生sorddarin,这表明与其他真菌目相比,Xylariales成员更频繁地产生sorddarin。
Distribution of the antifungal agents sordarins across filamentous fungi
Sordarins are a class of natural antifungal agents which act by specifically inhibiting fungal protein synthesis through their interaction with the elongation factor 2, EF2. A number of natural sordarins produced by diverse fungi of different classes have been reported in the literature. We have run an exhaustive search of sordarin-producing fungi using two different approaches consecutively, the first one being a differential sensitivity screen using a sordarin-resistant mutant yeast strain run in parallel with a wild type strain, and the second one an empiric screen against Candida albicans followed by early detection of sordarins by LC–MS analysis. Using these two strategies we have detected as many as 22 new strains producing a number of different sordarin analogues, either known (sordarin, xylarin, zofimarin) or novel (isozofimarin and 4′-O-demethyl sordarin). Sordarin and xylarin were the most frequently found compounds in the class. The producing strains were subjected to sequencing of the ITS region to determine their phylogenetic affinities. All the strains were shown to belong to the Xylariales, being distributed across three families in this order, the Xylariaceae, the Amphisphaeriaceae, and the Diatrypaceae. Despite being screened in large numbers, we did not find sordarin production in any other fungal group, including those orders where sordarin producing fungi are known to exist (i.e., Sordariales, Eurotiales, and Microascales), suggesting that the production of sordarin is a trait more frequently associated to members of the Xylariales than to any other fungal order.