Department of Animal Science, Faculty of Science and Technology, Aarhus University, Blichers Allé 20, Tjele, Denmark.
Environ Microbiol. 2012 May;14(5):1159-70. doi: 10.1111/j.1462-2920.2011.02696.x. Epub 2012 Jan 18.
Like many other filamentous fungi, Fusarium graminearum has the genetic potential to produce a vast array of unknown secondary metabolites. A promising approach to determine the nature of these is to activate silent secondary metabolite gene clusters through constitutive expression of cluster specific transcription factors. We have developed a system in which an expression cassette containing the transcription factor from the targeted PKS cluster disrupts the production of the red mycelium pigment aurofusarin. This aids with identification of mutants as they appear as white colonies and metabolite analyses where aurofusarin and its intermediates are normally among the most abundant compounds. The system was used for constitutive expression of the local transcription factor from the PKS9 cluster (renamed FSL) leading to production of three novel fusarielins, F, G and H. This group of compounds has not previously been reported from F. graminearum or linked to a biosynthetic gene in any fungal species. The toxicity of the three novel fusarielins was examined against colorectal cancer cell lines where fusarielin H was more potent than fusarielin F and G.
与许多其他丝状真菌一样，禾谷镰刀菌具有产生大量未知次生代谢物的遗传潜力。确定这些代谢物性质的一种很有前途的方法是通过组成型表达簇特异性转录因子来激活沉默的次生代谢物基因簇。我们开发了一种系统，其中包含目标 PKS 簇转录因子的表达盒会破坏红色菌丝体色素 aureofusarin 的产生。这有助于鉴定突变体，因为它们呈现白色菌落，并且代谢物分析表明 aureofusarin 及其中间产物通常是最丰富的化合物之一。该系统用于组成型表达 PKS9 簇的本地转录因子（重命名为 FSL），导致产生三种新型的 fusarielin，F、G 和 H。这组化合物以前从未在禾谷镰刀菌或任何真菌物种中的生物合成基因中报道过。还检测了三种新型 fusarielins 对结直肠癌细胞系的毒性，其中 fusarielin H 比 fusarielin F 和 G 更有效。
