A5030050971- Microbial Natural Products and Biosynthesis
- Mass Spectrometry Techniques and Applications
- Computational Drug Discovery Methods
- Metabolomics and Mass Spectrometry Studies
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Crystallization and Solubility Studies
- Water Quality Monitoring and Analysis
- Spectroscopy and Chemometric Analyses
- Bacterial Genetics and Biotechnology
- X-ray Diffraction in Crystallography
- Marine Sponges and Natural Products
- Plant biochemistry and biosynthesis
- Carbohydrate Chemistry and Synthesis
- Analytical Chemistry and Chromatography
- Fungal Biology and Applications
- Phytochemistry and Bioactive Compounds
- Ferrocene Chemistry and Applications
- Cancer therapeutics and mechanisms
- Antimicrobial Peptides and Activities
- vaccines and immunoinformatics approaches
- Chemical synthesis and alkaloids
- Microbial Metabolism and Applications
- Biochemical and Structural Characterization
- Plant Pathogenic Bacteria Studies
Simon Fraser University
2018-2024
Burnaby Hospital
2018-2021
McMaster University
2016
Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced product structures. Lack availability these data preventing implementation new technologies science. Specifically, development computational strategies for compound characterization and identification are being hampered by lack a comprehensive known compounds against which to compare experimental data. The creation an access,...
Few tools exist in natural products discovery to integrate biological screening and untargeted mass spectrometry data at the library scale. Previously, we reported Compound Activity Mapping as a strategy for predicting compound bioactivity profiles directly from primary results on extract libraries. We now present NP Analyst, an open online platform that accepts bioassay of almost any type, is compatible with major instrument manufacturers via mzML format. In addition, Analyst will accept...
The development of new "omics" platforms is having a significant impact on the landscape natural products discovery. However, despite advantages that such bring to field, there remains no straightforward method for characterizing chemical libraries using two-dimensional nuclear magnetic resonance (2D-NMR) experiments. NMR analysis provides powerful complement mass spectrometric approaches, given universal coverage high degree signal overlap, particularly in one-dimensional spectra, has...
Whole genome sequencing of a Burkholderiales strain library led to the discovery antifungal polyketide lagriamide B. Combining data from sequence, NMR experiments and computational predictions defined full absolute configuration.
Abstract The rapid emergence of antimicrobial resistance presents serious health challenges to the management infectious diseases, a problem that is further exacerbated by slowing rates drug discovery in recent years. phenomenon collateral sensitivity (CS), whereby one accompanied increased another, provides new opportunities address both these challenges. Here, we present high-throughput screening platform termed Collateral Sensitivity Profiling (CSP) map difference bioactivity large...
Polyketide or polyketide-like macrolides (pMLs) continue to serve as a source of inspiration for drug discovery. However, their inherent structural and stereochemical complexity challenges efforts explore related regions chemical space more broadly. Here, we report strategy termed the Targeted Sampling Natural Product (TSNaP) that is designed identify assess bounded by this important class molecules. Using TSNaP, family tetrahydrofuran-containing pMLs are computationally assembled from pML...
Two new lipopeptaibols, tolypocaibols A (1) and B (2), the mixed NRPS-polyketide-shikimate natural product maximiscin [(P/M)-3)] were isolated from a Tolypocladium sp. fungal endophyte of marine alga Spongomorpha arcta. Analysis NMR mass spectrometry data revealed amino acid sequences which both comprise 11 residues with valinol C-terminus decanoyl acyl chain at N-terminus. The configuration acids was determined by Marfey's analysis. Tolypocaibols (2) showed moderate, selective inhibition...
Ohmyungsamycin A and ecumicin are structurally related cyclic depsipeptide natural products that possess activity against Mycobacterium tuberculosis (Mtb), the causative agent of (TB). Herein, we describe design synthesis a library analogues these two using an efficient solid-phase late-stage macrolactamization strategy. Lead possessed potent Mtb in vitro (minimum inhibitory concentration 125-500 nM) were shown to inhibit protein degradation by mycobacterial ClpC1-ClpP1P2 protease with...
Bacterial natural products have found many important industrial applications. Yet traditional discovery pipelines often prioritize individual product families despite the presence of multiple biosynthetic gene clusters in each bacterial genome. Systematic characterization talented strains is a means to expand known space. Here, we report genomics, epigenomics, and metabolomics studies
Appending of ferrocene (Fc) to biologically-active organic backbones can generate novel multi-functional species for targeting bacteria and cancer. In this work Fc was linked coumarin anthraquinone with the goal harnessing redox-active centre new compounds that exhibit cytoxicity through generation toxic reactive oxygen (ROS). A Cu(I)-catalyzed azide-alkyne cycloaddition "click" reaction used connect components via a triazole linker. Cyclic voltammetry shows potentials are suitable oxidation...
Elucidating the mechanism of action (MoA) antibacterial natural products is crucial to evaluating their potential as novel antibiotics. Marinopyrroles, pentachloropseudilin, and pentabromopseudilin are densely halogenated, hybrid pyrrole-phenol with potent activity against Gram-positive bacterial pathogens like
bacteria have emerged as a promising source of structurally diverse natural products that are expected to play important ecological and industrial roles. This order ranks in the top three terms predicted product diversity from available genomes, warranting further genome sequencing efforts. However, major hurdle obtaining is biosynthetic genes often 'silent' or poorly expressed. Here we report complementary strain isolation, genomics, metabolomics, synthetic biology approaches enable...
The development of chemotherapies against eukaryotic pathogens is especially challenging because both the evolutionary conservation drug targets between host and parasite, evolution strain-dependent resistance. There a strong need for new nontoxic drugs with broad-spectrum activity trypanosome parasites such as Leishmania Trypanosoma. A relatively untested approach to target macromolecular interactions in rather than small molecular interactions, under hypothesis that features specifying...
We describe the synthesis and calcium-dependent antimicrobial activity of a small library glycinocin analogues that differ by variation in exocyclic fatty acyl substituent.
We present here the genome sequence ofStreptomyces canusATCC 12647, a producer of antibiotic telomycin, noted for its unique antibacterial activity against cardiolipin. Genomic analysis using bioinformatics tool PRISM revealed presence multiple biosynthetic gene clusters, including those telomycin and other natural products potential pharmacological interest.
High-throughput chemical analysis of natural product mixtures lags behind developments in genome sequencing technologies and laboratory automation, leading to a disconnect between library-scale biological profiling that limits new molecule discovery. Here, we report orthogonal sample multiplexing strategy can increase mass spectrometry-based up 30-fold over traditional methods. Profiled pooled samples undergo subsequent computational deconvolution reconstruct peak lists for each the set. We...
A bidirectional solid-phase strategy is described for the total synthesis of coralmycin and a desmethoxy analogue that possessed potent antibacterial activity.
Microorganisms from the order Burkholderiales have been source of a number important classes natural products in recent years. For example, study beetle-associated symbiont Burkholderia gladioli led to discovery antifungal polyketide lagriamide; an molecule perspectives both biotechnology and chemical ecology. As part wider project sequence genomes our in-house library we identified strain containing biosynthetic gene cluster (BGC) similar original lagriamide BGC. Structure prediction failed...