Metabolomics-based chemotaxonomy of root endophytic fungi for natural products discovery
TL;DR: The results provide an extensive resource to dereplicate fungal natural products and may assist future discovery programs by providing a guide for the selection of target fungi.
Abstract: Fungi are prolific producers of natural products routinely screened for biotechnological applications, and those living endophytically within plants attract particular attention because of their purported chemical diversity. However, the harnessing of their biosynthetic potential is hampered by a large and often cryptic phylogenetic and ecological diversity, coupled with a lack of large-scale natural products' dereplication studies. To guide efforts to discover new chemistries among root-endophytic fungi, we analyzed the natural products produced by 822 strains using an untargeted UPLC-ESI-MS/MS-based approach and linked the patterns of chemical features to fungal lineages. We detected 17 809 compounds of which 7951 were classified in 1992 molecular families, whereas the remaining were considered unique chemistries. Our approach allowed to annotate 1191 compounds with different degrees of accuracy, many of which had known fungal origins. Approximately 61% of the compounds were specific of a fungal order, and differences were observed across lineages in the diversity and characteristics of their chemistries. Chemical profiles also showed variable chemosystematic values across lineages, ranging from relative homogeneity to high heterogeneity among related fungi. Our results provide an extensive resource to dereplicate fungal natural products and may assist future discovery programs by providing a guide for the selection of target fungi.
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TL;DR: This is the first report of tsitsikammamines from the genus Latrunculia du Bocage and the successful application of molecular networking in the identification of comprehensive chemical inventory of L. biformis followed by targeted isolation of new molecules.
Abstract: The Antarctic deep-sea sponge Latrunculia (Latrunculia) biformis Kirkpatrick, 1908 (Class Demospongiae Sollas, Order Poecilosclerida Topsent, Latrunculiidae Topsent) was selected for chemical analyses due to its potent anticancer activity. Metabolomic analysis of its crude extract by HRMS/MS-based molecular networking showed the presence of several clusters of pyrroloiminoquinone alkaloids, i.e., discorhabdin and epinardin-type brominated pyridopyrroloquinolines and tsitsikammamines, the non-brominated bis-pyrroloiminoquinones. Molecular networking approach combined with a bioactivity-guided isolation led to the targeted isolation of the known pyrroloiminoquinone tsitsikammamine A (1) and its new analog 16,17-dehydrotsitsikammamine A (2). The chemical structures of the compounds 1 and 2 were elucidated by spectroscopic analysis (one-dimensional (1D) and two-dimensional (2D) NMR, HR-ESIMS). Due to minute amounts, molecular modeling and docking was used to assess potential affinities to potential targets of the isolated compounds, including DNA intercalation, topoisomerase I-II, and indoleamine 2,3-dioxygenase enzymes. Tsitsikammamines represent a small class of pyrroloiminoquinone alkaloids that have only previously been reported from the South African sponge genus Tsitsikamma Samaai & Kelly and an Australian species of the sponge genus Zyzzya de Laubenfels. This is the first report of tsitsikammamines from the genus Latrunculia du Bocage and the successful application of molecular networking in the identification of comprehensive chemical inventory of L.biformis followed by targeted isolation of new molecules. This study highlights the high productivity of secondary metabolites of Latrunculia sponges and may shed new light on their biosynthetic origin and chemotaxonomy.
37 citations
Cites methods from "Metabolomics-based chemotaxonomy of..."
...MN is a versatile method that has been used in many areas including drug discovery, ecology, microbiology, and biosynthesis [38,49,50]....
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24 citations
Cites background from "Metabolomics-based chemotaxonomy of..."
..., 2018), metabolomics (Hill et al., 2018;Maciá-Vicente et al., 2018), or combinations thereof (e....
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TL;DR: Deep-sea coral species have distinct metabolomic fingerprints and exhibit high metabolomic diversity at multiple scales which may contribute to their capabilities to respond to both natural and anthropogenic stressors, including climate change.
Abstract: From shallow water to the deep sea, corals form the basis of diverse communities with significant ecological and economic value. These communities face many anthropogenic stressors including energy and mineral extraction activities, ocean acidification and rising sea temperatures. Corals and their symbionts produce a diverse assemblage of compounds that may help provide resilience to some of these stressors. We aim to characterize the metabolomic diversity of deep-sea corals in an ecological context by investigating patterns across space and phylogeny. We applied untargeted Liquid Chromatography-Mass Spectrometry to examine the metabolomic diversity of the deep-sea coral, Callogorgia delta, across three sites in the Northern Gulf of Mexico as well as three other deep-sea corals, Stichopathes sp., Leiopathes glaberrima, and Lophelia pertusa, and a shallow-water species, Acropora palmata. Different coral species exhibited distinct metabolomic fingerprints and differences in metabolomic richness including core ions unique to each species. C. delta was generally least diverse while Lophelia pertusa was most diverse. C. delta from different sites had different metabolomic fingerprints and metabolomic richness at individual and population levels, although no sites exhibited unique core ions. Two core ions unique to C. delta were putatively identified as diterpenes and thus may possess a biologically important function. Deep-sea coral species have distinct metabolomic fingerprints and exhibit high metabolomic diversity at multiple scales which may contribute to their capabilities to respond to both natural and anthropogenic stressors, including climate change.
17 citations
TL;DR: Two new dimeric compounds of the alternariol class, (±) alternarlactones A (1) and B (2), were isolated along with 11 known compounds from the fungus Alternaria alternata P1210 to provide preliminary structure-activity relationship of this class of compounds against neglected tropical diseases.
Abstract: Two new dimeric compounds of the alternariol class, (±)-alternarlactones A (1) and B (2), were isolated along with 11 known compounds from the fungus Alternaria alternata P1210. Their structures were elucidated with the assistance of long-range HSQMBC to address inadequate cross-peaks in HMBC that result from the highly dense quaternary carbons, as well as theoretical calculations. All isolated altenuisol derivatives were screened for their antiparasitic activities, which provide a preliminary structure-activity relationship of this class of compounds against neglected tropical diseases.
16 citations
TL;DR: There is sufficient evidence for endophyte-derived plant metabolites, which could be pursued as alternative sources of commercially important plant metabolites as well as the contribution of plant and microbial metabolomics for answering fundamental questions of plant-endophyte interaction.
Abstract: Among the various plant-associated microbiota, endophytes (the microbial communities inhabiting plant endosphere without causing disease symptoms) exhibit the most intimate and specific association with host plants. Endophytic microbes influence various aspects of plant responses (such as increasing availability of nutrients, tolerance against biotic and abiotic stresses, etc.) by modulating the primary and secondary metabolism of the host. Besides, endophytic microbes produce a diverse array of bioactive compounds, which have potential applications in the pharmaceutical, food, and cosmetic industries. Further, there is sufficient evidence for endophyte-derived plant metabolites, which could be pursued as alternative sources of commercially important plant metabolites. The field of bioprospecting, the discovery of novel chemistries, and endophyte-mediated production of plant metabolites have witnessed a boom with the advent of omics technologies (especially metabolomics) in endophyte research. The high throughput study of small metabolites at a particular timepoint or tissue forms the core of metabolomics. Being downstream to transcriptome and proteome, the metabolome provides the most direct reflection of the phenotype of an organism. The contribution of plant and microbial metabolomics for answering fundamental questions of plant-endophyte interaction, such as the effect of endophyte inoculation on plant metabolome, composition of metabolites on the impact of environmental stressors (biotic and abiotic), etc., have also been discussed.
16 citations
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TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.
88,255 citations
"Metabolomics-based chemotaxonomy of..." refers methods in this paper
...Isolates were then grouped into OTUs according to ITS similarity of at least 97% using the BLASTClust tool from BLAST (Altschul et al., 1990), and a consensus taxonomy was assigned to each OTU based on the isolates’ identifications....
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TL;DR: Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
Abstract: Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
32,980 citations
"Metabolomics-based chemotaxonomy of..." refers methods in this paper
...0 (Shannon et al., 2003), and further statistical analyses were performed in R with aid of relevant packages....
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...4.0 (Shannon et al., 2003), and further statistical analyses were performed in R with aid of relevant packages....
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University of Michigan1, University of Massachusetts Amherst2, University of New Mexico3, University of British Columbia4, Texas A&M University5, University of Minnesota6, University of Warwick7, Dalhousie University8, Colorado School of Mines9, University of Ljubljana10, Graz University of Technology11, Louisiana State University12
TL;DR: M mothur is used as a case study to trim, screen, and align sequences; calculate distances; assign sequences to operational taxonomic units; and describe the α and β diversity of eight marine samples previously characterized by pyrosequencing of 16S rRNA gene fragments.
Abstract: mothur aims to be a comprehensive software package that allows users to use a single piece of software to analyze community sequence data. It builds upon previous tools to provide a flexible and powerful software package for analyzing sequencing data. As a case study, we used mothur to trim, screen, and align sequences; calculate distances; assign sequences to operational taxonomic units; and describe the alpha and beta diversity of eight marine samples previously characterized by pyrosequencing of 16S rRNA gene fragments. This analysis of more than 222,000 sequences was completed in less than 2 h with a laptop computer.
17,350 citations
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...34.4 (Wang et al., 2007; Schloss et al., 2009)....
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TL;DR: The RDP Classifier can rapidly and accurately classify bacterial 16S rRNA sequences into the new higher-order taxonomy proposed in Bergey's Taxonomic Outline of the Prokaryotes, and the majority of the classification errors appear to be due to anomalies in the current taxonomies.
Abstract: The Ribosomal Database Project (RDP) Classifier, a naive Bayesian classifier, can rapidly and accurately classify bacterial 16S rRNA sequences into the new higher-order taxonomy proposed in Bergey's Taxonomic Outline of the Prokaryotes (2nd ed., release 5.0, Springer-Verlag, New York, NY, 2004). It provides taxonomic assignments from domain to genus, with confidence estimates for each assignment. The majority of classifications (98%) were of high estimated confidence (≥95%) and high accuracy (98%). In addition to being tested with the corpus of 5,014 type strain sequences from Bergey's outline, the RDP Classifier was tested with a corpus of 23,095 rRNA sequences as assigned by the NCBI into their alternative higher-order taxonomy. The results from leave-one-out testing on both corpora show that the overall accuracies at all levels of confidence for near-full-length and 400-base segments were 89% or above down to the genus level, and the majority of the classification errors appear to be due to anomalies in the current taxonomies. For shorter rRNA segments, such as those that might be generated by pyrosequencing, the error rate varied greatly over the length of the 16S rRNA gene, with segments around the V2 and V4 variable regions giving the lowest error rates. The RDP Classifier is suitable both for the analysis of single rRNA sequences and for the analysis of libraries of thousands of sequences. Another related tool, RDP Library Compare, was developed to facilitate microbial-community comparison based on 16S rRNA gene sequence libraries. It combines the RDP Classifier with a statistical test to flag taxa differentially represented between samples. The RDP Classifier and RDP Library Compare are available online at http://rdp.cme.msu.edu/.
16,048 citations
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...34.4 (Wang et al., 2007; Schloss et al., 2009)....
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01 Jan 2007
10,427 citations
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...2-1 (Oksanen et al., 2015)....
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