Department of Chemistry , University of Zurich , Winterthurerstrasse 190 , Zurich , CH 8057 , Switzerland.
Department of Chemistry , University of Illinois at Urbana-Champaign , 600 South Mathews Avenue , Urbana , Illinois 61801 , United States.
J Nat Prod. 2020 Feb 28;83(2):438-446. doi: 10.1021/acs.jnatprod.9b00986. Epub 2020 Jan 28.
The toxicity of the cyanobacterium EAWAG 127a was evaluated against the sensitive grazer , and the extract possessed strong activity. To investigate the compounds responsible for cytotoxicity, a series of peptides from this cyanobacterium were studied using a combined genomic and molecular networking approach. The results led to the isolation, structure elucidation, and biological evaluation of microviridin 1777, which represents the most potent chymotrypsin inhibitor characterized from this family of peptides to date. Furthermore, the biosynthetic gene clusters of microviridin, anabaenopeptin, aeruginosin, and piricyclamide were located in the producing organism, and six additional natural products were identified by tandem mass spectrometry analyses. These results highlight the potential of modern techniques for the identification of natural products, demonstrate the ecological role of protease inhibitors produced by cyanobacteria, and raise ramifications concerning the presence of novel, yet uncharacterized, toxin families in cyanobacteria beyond microcystin.
评估了对敏感食草动物具有毒性的蓝藻 EAWAG 127a，提取物具有很强的活性。为了研究导致细胞毒性的化合物，使用基因组和分子网络组合方法研究了这种蓝藻的一系列肽。研究结果导致了微病毒素 1777 的分离、结构阐明和生物学评价，这是迄今为止从该肽家族中鉴定出的最有效的胰凝乳蛋白酶抑制剂。此外，微病毒素、鱼腥藻肽、鱼腥藻素和吡咯西酰胺的生物合成基因簇位于产生菌中，并通过串联质谱分析鉴定了另外六种天然产物。这些结果突出了现代技术用于鉴定天然产物的潜力，证明了蓝藻产生的蛋白酶抑制剂的生态作用，并提出了关于蓝藻中除微囊藻毒素以外存在新型但尚未表征的毒素家族的问题。
