Dereplication of microbial metabolites through database search of mass spectra

Abstract

Natural products have traditionally been rich sources for drug discovery. In order to clear the road toward the discovery of unknown natural products, biologists need dereplication strategies that identify known ones. Here we report DEREPLICATOR+, an algorithm that improves on the previous approaches for identifying peptidic natural products, and extends them for identification of polyketides, terpenes, benzenoids, alkaloids, flavonoids, and other classes of natural products. We show that DEREPLICATOR+ can search all spectra in the recently launched Global Natural Products Social molecular network and identify an order of magnitude more natural products than previous dereplication efforts. We further demonstrate that DEREPLICATOR+ enables cross-validation of genome-mining and peptidogenomics/glycogenomics results.

Feature-based Molecular Networking in the GNPS Analysis Environment

“…The use of these tools with the MS 2 spectral summary file enables subsequent direct mapping of these annotations to the molecular networks produced by the feature-based molecular networking method. These tools include SIRIUS 22 , DEREPLICATOR, 39,40 NAP, 19 MS2LDA 20 , MolNetEnhancer 21 (see Supplementary Note 5), as well as other software such as MetWork 41 , CFM-ID 42 , MetGem 43 , MetFrag 44 .…”

Metabolic and metagenomic profiling of hydrocarbon-degrading microorganisms obtained from the deep biosphere of the Gulf of México

“…It is estimated that over twenty thousand molecules have been discovered from marine sources (Gerwick and Moore 2012) High-resolution tandem MS (HR-MS/MS)-based metabolomics has demonstrated to be a powerful tool to inventory the chemistry derived from microbe's cultures (Floros et al 2016). This technique could generate a large amount of data containing known and new molecules that when coupled to appropriate computational tools could lead to a rapid dereplication (i.e., identification of known molecules) process (Mohimani et al 2018). In this regard, the Global Natural Product Social (GNPS) molecular networking platform has contributed to the abovementioned process as well as to the discovery of new chemical entities in a more rapid and precise manner compared to other conventional computational approaches (Quinn et al 2017).…”

Tools and resources for metabolomics research community: A 2017–2018 update

“…For instance, for annotation of untargeted LC–MS data, the challenges are nicely explained, where in silico fragmentation tools such as MS‐FINDER, CFM‐ID, MetFrag, ChemDistiller, and Compound Structure Identification (CSI):FingerID that can annotate compounds from existing structure databases and are used in the critical assessment of small molecule identification contests are introduced and discussed . Databases such as chemical structure databases such as PubChem (≈83 million compounds), ChemSpider (≈58 million compounds), ChEMBL (2.1 million compounds), ChemBank (1.2 million compounds), ChEBI (440,000 compounds), Dictionary of Natural Products (≈300 thousand compounds), AntiMarin (≈60 thousand compounds), Kyoto Encyclopedia of Genes and Genomes (KEGG; ≈16 thousand compounds), MetaCy (≈10 thousand compounds), mzCloud (≈3 thousand compounds), NuBBEDB (2500 compounds), MIBiG (≈1600 compounds), DrugBank (1360 compounds with structural information), and Norine (≈1000 compounds) have facilitated annotations of metabolites and natural products over a few decades . Capabilities of tools such as METLIN for annotation of both known and unknown metabolites continue to expand .…”

“…DEREPLICATOR+ is an algorithm that improves on the previous approaches for identifying peptidic natural products and extends them for identification of polyketides, terpenes, benzenoids, alkaloids, flavonoids, and other classes of natural products . It is a standalone tool, and also offers a web application.…”