Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, building E8.1, 66123, Saarbrücken, Germany.
German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124, Braunschweig, Germany.
Angew Chem Int Ed Engl. 2017 Aug 1;56(32):9614-9618. doi: 10.1002/anie.201704790. Epub 2017 Jul 5.
In the search for new secondary metabolites from myxobacteria, a strain from the genus Pyxidicoccus was investigated. This led to the identification of a new class of natural products showing structural novelty and interesting biological activity. Isolation and structure elucidation of two analogues led to the identification of pyxipyrrolone A and B, harboring the novel 3-methylene-2,3,4,5,6,7,8,9-octahydro-1H-benzo[e]isoindol-1-one scaffold. Mosher's ester analysis combined with NMR studies allowed the determination of all stereocenters but one. Genome sequencing of the producer strain led to the identification of a putative biosynthetic gene cluster for the pyxipyrrolones. The compounds showed activity against several cancer cell lines (μm range) with pyxipyrrolone B having 2- to 11-fold higher activity than A, although they differ only by one methylene group.
在从粘细菌中寻找新的次生代谢产物的过程中，研究了Pyxidicoccus 属的一株菌。这导致了一类具有新颖结构和有趣生物活性的新型天然产物的鉴定。两种类似物的分离和结构阐明导致了pyxipyrrolone A 和 B 的鉴定，它们含有新颖的 3-亚甲基-2,3,4,5,6,7,8,9-八氢-1H-苯并[e]异吲哚-1-酮支架。Mosher 酯分析结合 NMR 研究允许确定除一个以外的所有立体中心。生产菌株的基因组测序导致了对 pyxipyrrolones 生物合成基因簇的鉴定。这些化合物对几种癌细胞系（μm 范围）表现出活性，其中 pyxipyrrolone B 的活性比 A 高 2 到 11 倍，尽管它们仅相差一个亚甲基。
