A5074380646- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Metabolomics and Mass Spectrometry Studies
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- DNA Repair Mechanisms
- Chemical synthesis and alkaloids
- Species Distribution and Climate Change
- Catalytic Alkyne Reactions
- Analytical Chemistry and Chromatography
- Isotope Analysis in Ecology
- Chromium effects and bioremediation
- Signaling Pathways in Disease
- Protist diversity and phylogeny
- Synthesis and Biological Activity
- Glutathione Transferases and Polymorphisms
- Microbial Community Ecology and Physiology
- Phytoplasmas and Hemiptera pathogens
- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Catalytic Cross-Coupling Reactions
- Trypanosoma species research and implications
- Polyamine Metabolism and Applications
- Phytochemical compounds biological activities
- Genomics, phytochemicals, and oxidative stress
Université de Sherbrooke
2025
University of California, San Diego
2012-2024
Scripps Institution of Oceanography
2012-2024
University of Mississippi
2021-2024
Harvard University
2017-2019
Treasury Board of Canada Secretariat
2017
IIT@MIT
2016
Massachusetts Institute of Technology
2015
A major goal in natural product discovery programs is to rapidly dereplicate known entities from complex biological extracts. We demonstrate here that molecular networking, an approach organizes MS/MS data based on chemical similarity, a powerful complement traditional dereplication strategies. Successful with networks requires spectra of the mixture along standards, synthetic compounds, or well-characterized organisms, preferably organized into robust databases. This can accommodate...
Certain Escherichia coli strains residing in the human gut produce colibactin, a small-molecule genotoxin implicated colorectal cancer pathogenesis. However, colibactin's chemical structure and molecular mechanism underlying its genotoxic effects have remained unknown for more than decade. Here we combine an untargeted DNA adductomics approach with synthesis to identify characterize covalent modification from cell lines treated colibactin-producing E. Our data establish that colibactin...
Integrating LC-MS/MS molecular networking and bioassay-guided fractionation enabled the targeted isolation of a new bioactive cyclic octapeptide, samoamide A (1), from sample cf. Symploca sp. collected in American Samoa. The structure 1 was established by detailed 1D 2D NMR experiments, HRESIMS data, chemical degradation/chromatographic (e.g., Marfey's analysis) studies. Pure compound shown to have vitro cytotoxic activity against several human cancer cell lines both traditional culture zone...
Bastimolide A (1), a polyhydroxy macrolide with 40-membered ring, was isolated from new genus of the tropical marine cyanobacterium Okeania hirsuta. This novel defined by spectroscopy and chemical reactions to possess one 1,3-diol, 1,3,5-triol, six 1,5-diols, tert-butyl group; however, relationships these moieties another were obscured highly degenerate 1H NMR spectrum. Its complete structure absolute configuration therefore unambiguously determined X-ray diffraction analysis...
Certain commensal and pathogenic bacteria produce colibactin, a small-molecule genotoxin that causes interstrand cross-links in host cell DNA. Although colibactin alkylates DNA, the molecular basis for cross-link formation is unclear. Here, we report biosynthetic enzyme ClbL an amide bond-forming links aminoketone β-keto thioester substrates vitro vivo. The substrate specificity of strongly supports role this terminating NRPS-PKS assembly line incorporating two electrophilic cyclopropane...
Gallinamide A, originally isolated with a modest antimalarial activity, was subsequently reisolated and characterized as potent, selective, irreversible inhibitor of the human cysteine protease cathepsin L. Molecular docking identified potential modifications to improve binding, which were synthesized suite analogs. Resultingly, this current study produced most potent gallinamide analog yet tested against L (10, Ki = 0.0937 ± 0.01 nM kinact/Ki 8 730 000). From protein structure substrate...
Abstract Even though raw mass spectrometry data is information rich, the vast majority of underutilized. The ability to interrogate these rich datasets handicapped by limited capability and flexibility existing software. We introduce Mass Spec Query Language (MassQL) that addresses issues enabling an expressive set patterns be queried directly from data. MassQL open-source query language for flexible spectrometer manufacturer-independent mining MS envision flexibility, scalability, ease use...
The viequeamides, a family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, were isolated from shallow subtidal collection "button" cyanobacterium (Rivularia sp.) near the island Vieques, Puerto Rico. Planar structures two major compounds, viequeamide A (1) and B (2), elucidated by 2D-NMR spectroscopy mass spectrometry, whereas absolute configurations determined traditional hydrolysis, derivative formation, chromatography in comparison with standards. In...
Coral reefs are intricate ecosystems that harbor diverse organisms, including 25% of all marine fish. Healthy corals exhibit a complex symbiosis between coral polyps, endosymbiotic alga, and an array microorganisms, called the holobiont. Secretion specialized metabolites by microbiota is thought to contribute defense this sessile organism against harmful biotic abiotic factors. While few causative agents diseases have been unequivocally identified, fungi implicated in massive destruction...
The tropical marine cyanobacterium Moorena producens JHB is a prolific source of secondary metabolites with potential biomedical utility. Previous studies on this strain led to the discovery several novel compounds such as hectochlorins and jamaicamides. However, bioinformatic analyses its genome indicate presence numerous cryptic biosynthetic gene clusters that have yet be characterized. To potentially stimulate production from strain, it was cocultured Candida albicans. From experiment, we...
Abstract Background LGR5, an intestinal stem cell marker, is crucial in mediating R-spondin (RSPO) signaling, supporting canonical WNT signaling for tissue development and renewal. This pathway pivotal gastrointestinal (GI) disease, assisting wound healing playing a role cancer progression chemoresistance. While modulating the holds therapeutic potential, directly targeting it risks disrupting differentiation organ function. whose activity complements but does not fully overlap with pathway,...
A two-stage "tandem strategy" for the regiocontrolled synthesis of very highly substituted quinolines is described. Benzannulation based on reaction cyclobutenones or diazo ketones with N-propargyl-substituted ynamides proceeds via a cascade several pericyclic reactions to generate multiply aniline derivatives. In second stage tandem strategy, triflate derivatives phenolic benzannulation products undergo Larock cyclization upon exposure iodine form that are further elaborated by methods such...
Moorea producens JHB, a Jamaican strain of tropical filamentous marine cyanobacteria, has been extensively studied by traditional natural products techniques. These previous bioassay and structure guided isolations led to the discovery two exciting classes products, hectochlorin (1) jamaicamides A (2) B (3). In current study, mass spectrometry-based ‘molecular networking’ was used visualize metabolome both enhanced isolation workflow, revealing additional metabolites in these compound...
The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences gene expression cultured macrophages following treatment. This analysis led the hypothesis that exerts anti-inflammatory activity through activation cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile element (ARE/EpRE) signaling pathway. Activation...
Bacteria have evolved various strategies to combat heavy metal stress, including the secretion of small molecules, known as metallophores. These molecules hold a potential role in mitigation toxic contamination from environment (bioremediation). Herein, we employed combined comparative metabolomic and genomic analyses study metallophores excreted by Delftia lacustris DSM 21246. LCMS-metabolomic analysis this bacterium cultured under iron limitation led suite lipophilic exclusively secreted...
A collection of the tropical marine cyanobacterium Symploca sp., collected near Kimbe Bay, Papua New Guinea, previously yielded several new metabolites including kimbeamides A–C, kimbelactone A, and tasihalide C. Investigations into a more polar cytotoxic fraction three lipopeptides, tasiamides C–E (1–3). The planar structures were deduced by 2D NMR spectroscopy tandem mass spectrometry, their absolute configurations determined combination Marfey's chiral-phase GC-MS analysis. These are...
Luquilloamides A-G (1-7) were isolated from a small environmental collection of marine cyanobacterium found growing on eelgrass (Zostera sp.) near Luquillo, Puerto Rico. Structure elucidation the luquilloamides was accomplished via detailed NMR and MS analyses, absolute configurations determined using combination advanced Mosher's method, J-based configuration analysis, semisynthetic fragment analysis derived ozonolysis, methylation, Baeyer-Villiger oxidation, esterification, specific...
Cupriavidus necator H16 is known to be a rich source of linear lipopeptide siderophores when grown under iron-depleted conditions; prior literature termed these compounds cupriachelins. These small molecules bear β -hydroxyaspartate moieties that contribute photoreduction iron bound as ferric cupriachelin. Here, we present structural assignment cupriachelins from C. B-4383 limitation. The characterization based on MS/MS fragmentation analysis, which was confirmed by 1D- and 2D-NMR for the...
ABSTRACT Certain commensal and pathogenic bacteria produce colibactin, a small molecule genotoxin that causes interstrand cross-links in host cell DNA. Though colibactin has been found to alkylate DNA, the molecular basis for cross-link formation is unclear. Here, we report biosynthetic enzyme ClbL an amide bond-forming links aminoketone β-keto thioester substrates vitro vivo . The substrate specificity of strongly supports role this terminating NRPS-PKS assembly line. This transformation...