Bohnert Markus, Nützmann Hans-Wilhelm, Schroeckh Volker, Horn Fabian, Dahse Hans-Martin, Brakhage Axel A, Hoffmeister Dirk
Department Pharmaceutical Biology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität Jena, Beutenbergstrasse 11a, 07745 Jena, Germany.
Department Molecular and Applied Microbiology, Leibniz-Institute for Infection Biology and Natural Product Research - Hans-Knöll-Institute, Beutenbergstrasse 11a, 07745 Jena, Germany.
Phytochemistry. 2014 Sep;105:101-8. doi: 10.1016/j.phytochem.2014.05.009. Epub 2014 Jun 3.
The fungal genus Armillaria is unique in that it is the only natural source of melleolide antibiotics, i.e., protoilludene alcohols esterified with orsellinic acid or its derivatives. This class of natural products is known to exert antimicrobial and cytotoxic effects. Here, we present a refined relationship between the structure and the antimicrobial activity of the melleolides. Using both agar diffusion and broth dilution assays, we identified the Δ(2,4)-double bond of the protoilludene moiety as a key structural feature for antifungal activity against Aspergillus nidulans, Aspergillus flavus, and Penicillium notatum. These findings contrast former reports on cytotoxic activities and may indicate a different mode of action towards susceptible fungi. We also report the isolation and structure elucidation of five melleolides (6'-dechloroarnamial, 6'-chloromelleolide F, 10-hydroxy-5'-methoxy-6'-chloroarmillane, and 13-deoxyarmellides A and B), along with the finding that treatment with an antifungal melleolide impacts transcription of A. nidulans natural product genes.
蜜环菌属真菌很独特，因为它是蜜环菌素类抗生素的唯一天然来源，即与苔色酸或其衍生物酯化的原伊鲁烯醇。已知这类天然产物具有抗菌和细胞毒性作用。在此，我们阐述了蜜环菌素的结构与抗菌活性之间的精细关系。通过琼脂扩散法和肉汤稀释法，我们确定原伊鲁烯部分的Δ(2,4)-双键是对构巢曲霉、黄曲霉和青霉具有抗真菌活性的关键结构特征。这些发现与之前关于细胞毒性活性的报道形成对比，可能表明对敏感真菌的作用方式不同。我们还报告了五种蜜环菌素（6'-脱氯蜜环菌甲素、6'-氯蜜环菌素F、10-羟基-5'-甲氧基-6'-氯蜜环烷以及13-脱氧蜜环菌素A和B）的分离和结构解析，同时发现用一种抗真菌蜜环菌素处理会影响构巢曲霉天然产物基因的转录。
