Qin Zhiwei, Munnoch John T, Devine Rebecca, Holmes Neil A, Seipke Ryan F, Wilkinson Karl A, Wilkinson Barrie, Hutchings Matthew I
Department of Molecular Microbiology , John Innes Centre , Norwich Research Park , Norwich , NR4 7UH , UK . Email:
School of Biological Sciences , University of East Anglia , Norwich Research Park , Norwich , NR4 7TJ , UK . Email:
Chem Sci. 2017 Apr 1;8(4):3218-3227. doi: 10.1039/c6sc04265a. Epub 2017 Feb 13.
We report a new species named that was isolated from the African fungus-growing plant-ant and show that it produces novel pentacyclic polyketides that are active against MRSA and VRE. The chemical scaffold of these compounds, which we have called the formicamycins, is similar to the fasamycins identified from the heterologous expression of clones isolated from environmental DNA, but has significant differences that allow the scaffold to be decorated with up to four halogen atoms. We report the structures and bioactivities of 16 new molecules and show, using CRISPR/Cas9 genome editing, that biosynthesis of these compounds is encoded by a single type 2 polyketide synthase biosynthetic gene cluster in the genome. Our work has identified the first antibiotic from the system and highlights the benefits of exploring unusual ecological niches for new actinomycete strains and novel natural products.
我们报道了一种新物种,它是从非洲培育真菌的切叶蚁中分离出来的,并表明它能产生对耐甲氧西林金黄色葡萄球菌(MRSA)和耐万古霉素肠球菌(VRE)有活性的新型五环聚酮化合物。我们将这些化合物的化学骨架称为甲酸霉素,它与从环境DNA中分离的克隆的异源表达中鉴定出的法沙霉素相似,但存在显著差异,这使得该骨架最多可被四个卤原子修饰。我们报道了16种新分子的结构和生物活性,并通过CRISPR/Cas9基因组编辑表明,这些化合物的生物合成由基因组中的一个单一的II型聚酮合酶生物合成基因簇编码。我们的工作鉴定出了来自该系统的第一种抗生素,并突出了探索不寻常生态位以寻找新的放线菌菌株和新型天然产物的益处。