Targeted Dereplication of Microbial Natural Products by High-Resolution MS and Predicted LC Retention Time
journal contributionposted on 26.04.2017, 19:14 by Justine Chervin, Marc Stierhof, Ming Him Tong, Doe Peace, Kine Østnes Hansen, Dagmar Solveig Urgast, Jeanette Hammer Andersen, Yi Yu, Rainer Ebel, Kwaku Kyeremeh, Veronica Paget, Gabriela Cimpan, Albert Van Wyk, Hai Deng, Marcel Jaspars, Jioji N. Tabudravu
A new strategy for the identification of known compounds in Streptomyces extracts that can be applied in the discovery of natural products is presented. The strategy incorporates screening a database of 5555 natural products including 5098 structures from Streptomyces sp., using a high-throughput LCMS data processing algorithm that utilizes HRMS data and predicted LC retention times (tR) as filters for rapid identification of known compounds in the natural product extract. The database, named StrepDB, contains for each compound the structure, molecular formula, molecular mass, and predicted LC retention time. All identified compounds are annotated and color coded for easier visualization. It is an indirect approach to quickly assess masses (which are not annotated) that may potentially lead to the discovery of new or novel structures. In addition, a spectral database named MbcDB was generated using the ACD/Spectrus DB Platform. MbcDB contains 665 natural products, each with structure, experimental HRESIMS, MS/MS, UV, and NMR spectra. StrepDB was used to screen a mutant Streptomyces albus extract, which led to the identification and isolation of two new compounds, legonmaleimides A and B, the structures of which were elucidated with the aid of MbcDB and spectroscopic techniques. The structures were confirmed by computer-assisted structure elucidation (CASE) methods using ACD/Structure Elucidator Suite. The developed methodology suggests a pipeline approach to the dereplication of extracts and discovery of novel natural products.
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t RLC retention timescompoundpipeline approachTargeted Dereplicationidentificationspectroscopic techniquesHRMS datanovel structuresMicrobial Natural ProductsNMR spectraUVstructure elucidationStreptomyces extractsACDHRESIMSStreptomyces albushigh-throughput LCMS data processing algorithmDBLC retention timeHigh-Resolution MSPredicted LC Retention TimeMbcDB5098 structures