Burning the Hay to Find the Needle – Data Mining Strategies in Natural Product Dereplication

Abstract

The acquisition and use of data from the LC/MS-ELSD analysis of extracts is described. The methodology requires MS spectra to be recorded in the positive/negative ESI mode, as well as the determination of retention time and peak area from ELSD. Subsequent calculation of molecular weight, referenced retention time, and normalized peak area, results in the creation of a peak library, which can be used for different data mining strategies: i) the dereplication of previously isolated natural products; ii) clustering/ranking of extracts for the creation of highly diverse natural product libraries; iii) a selection tool for the focused isolation of bioactive natural products and iv) to search for alternative sources of a target natural product.

A Strategy for the Rapid Identification of Fungal Metabolites and the Discovery of the Antiviral Activity of Pyrenocine a and Harzianopyridone

“…This is particularly true when dereplication of secondary metabolites in extracts of biological matrixes is unfeasible by high-resolution and high--throughput chromatography-spectroscopy hyphenated tools, such as HPLC-HRMS, HPLC-NMR and related techniques. [3][4][5][6][7] Data obtained from joint UV, LRMS and 1 H NMR analyses only, and sometimes 13 C NMR, can be used in querying databases such as the Dictionary of Natural Products (DNP), Antimarin, MarinLit, and Molecular Networking, as an effective combination for the rapid identification of known structures. 8,9 The rapid identification of secondary metabolites enables further assessment of structures of interest, particularly of unprecedentedly bioactive known compounds.…”

Bioactive Polyesters in Marine and Plant Endophytic Fungi

“…There are numerous approaches to dereplication based on hyphenated techniques, and each has its own advantages, be they sensitivity, resolution, or scale (mg vs μg) [7]. The most common approaches are LC-UV, LC-MS, LC-MS/MS and LC-NMR, or combinations thereof, and the increasing use of capillary and cryo-NMR probes [8][9][10][11][12][13][14][15][16]. Of course, any technique involving mass spectrometry will always potentially suffer from problems associated with ionization (or lack thereof) of the compounds being studied.…”

Electrospray Ionization Tandem Mass Spectrometry as a Tool for the Structural Elucidation and Dereplication of Natural Products: An Overview

“…Dereplication is the process that allows for the rapid identification of bioactive metabolites in crude extracts by distinguishing previously identified compounds from novel ones . This technique avoids repetitive work of isolation of already known NPs (Wolf & Siems, 2007), promoting chemical screening or metabolite profiling . The dereplication process involves separation of single metabolites by chromatographic methods, identification of these compounds by spectroscopic methods, bioassays for evaluation of the biological activity, and searches in databases for verification of the novelty of these compounds (Konishi et al, 2007;Wolf & Siems, 2007).…”

“…This technique avoids repetitive work of isolation of already known NPs (Wolf & Siems, 2007), promoting chemical screening or metabolite profiling . The dereplication process involves separation of single metabolites by chromatographic methods, identification of these compounds by spectroscopic methods, bioassays for evaluation of the biological activity, and searches in databases for verification of the novelty of these compounds (Konishi et al, 2007;Wolf & Siems, 2007). Hyphenated techniques have played a key role in the identification of NPs and other organic compounds Prasain et al, 2003).…”