Marner Michael, Hartwig Christoph, Patras Maria A, Wodi Stevy I M, Rieuwpassa Frets J, Ijong Frans G, Balansa Walter, Schäberle Till F
Institute for Insect Biotechnology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
Faculty of Fisheries and Marine Science, Jenderal Soedirman University, Purwokerto 53122, Indonesia.
Mar Drugs. 2020 Dec 17;18(12):649. doi: 10.3390/md18120649.
The discovery of novel natural products (NPs) that will serve as lead structures has to be an ongoing effort to fill the respective development pipelines. However, identification of NPs, which possess a potential for application in e.g., the pharma or agro sector, must be as cost effective and fast as possible. Furthermore, the amount of sample available for initial testing is usually very limited, not least because of the fact that the impact on the environment, i.e., the sampled biosystem, should be kept minimal. Here, our pipeline SeaPEPR is described, in which a primary bioactivity screening of crude extracts is combined with the analysis of their metabolic fingerprint. This enabled prioritization of samples for subsequent microfractionation and dereplication of the active compounds early in the workflow. As a case study, 76 marine sponge-derived extracts were screened against a microbial screening panel. Thereunder, human pathogenic bacteria ( ATCC35218 and ATCC33592) and yeast ( FH2173), as well as the phytopathogenic fungus MUCL45407. Overall, nine extracts revealed activity against at least one test organism. Metabolic fingerprinting enabled assigning four active extracts into one metabolic group; therefore, one representative was selected for subsequent microfractionation. Dereplication of the active fractions showed a new dibrominated aplysinopsin and a hypothetical chromazonarol stereoisomer derivative. Furthermore, inhibitory activity against the common plant pest was discovered for NPs of marine origin.
发现可作为先导结构的新型天然产物（NP）必须是一项持续的工作，以充实各自的开发流程。然而，鉴定具有在例如制药或农业领域应用潜力的NP必须尽可能具有成本效益且快速。此外，可用于初始测试的样品量通常非常有限，这尤其是因为对环境（即采样的生物系统）的影响应保持最小。在此，我们描述了我们的流程SeaPEPR，其中粗提物的初步生物活性筛选与它们的代谢指纹分析相结合。这使得能够在工作流程早期对样品进行优先排序，以便随后进行微分离和活性化合物的去重复。作为一个案例研究，针对一个微生物筛选小组对76种海洋海绵衍生提取物进行了筛选。其中包括人类病原菌（ATCC35218和ATCC33592）和酵母（FH2173），以及植物致病真菌MUCL45407。总体而言，九种提取物对至少一种测试生物体显示出活性。代谢指纹分析能够将四种活性提取物归为一个代谢组；因此，选择了一种代表性提取物进行后续微分离。活性级分的去重复显示出一种新的二溴化阿朴辛和一种假定的色唑诺醇立体异构体衍生物。此外，还发现了海洋来源的NP对常见植物害虫的抑制活性。
