A5066776722- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Genomics and Phylogenetic Studies
- Synthesis and Biological Activity
- Metabolomics and Mass Spectrometry Studies
- Plant Pathogens and Fungal Diseases
- Synthetic Organic Chemistry Methods
- Chemical synthesis and alkaloids
- Insect symbiosis and bacterial influences
- Chemical Synthesis and Analysis
- Bioactive Compounds and Antitumor Agents
- Insect and Arachnid Ecology and Behavior
- Cancer therapeutics and mechanisms
- Fungal Biology and Applications
- Analytical Chemistry and Chromatography
- Microbial Metabolic Engineering and Bioproduction
- Crystallization and Solubility Studies
- Phytochemistry and Bioactive Compounds
- X-ray Diffraction in Crystallography
- Phytochemical Studies and Bioactivities
- Tuberculosis Research and Epidemiology
- Plant biochemistry and biosynthesis
- Carbohydrate Chemistry and Synthesis
- Gut microbiota and health
- Steroid Chemistry and Biochemistry
University of Wisconsin–Madison
2016-2025
University of Wisconsin Carbone Cancer Center
2024-2025
Screen
2025
Pharmaceutical Biotechnology (Czechia)
2017
Madison Group (United States)
2017
University of Utah
2002-2012
University of Copenhagen
2012
Harvard University
2012
Kookmin University
2012
University of Kentucky
2012
Abstract Antimicrobial resistance is a global health crisis and few novel antimicrobials have been discovered in recent decades. Natural products, particularly from Streptomyces , are the source of most antimicrobials, yet discovery campaigns focusing on soil largely rediscover known compounds. Investigation understudied symbiotic sources has seen some success, no studies systematically explored microbiomes for antimicrobials. Here we assess distinct evolutionary lineages insect as new...
New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging microbiomes marine animals cutting-edge metabolomics genomic tools, we identified encouraging lead molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent vitro mouse-model efficacy toward multiple-drug-resistant pathogens, exhibits a wide safety index, functions through fungal-specific...
Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative systematically document links between metabolome (meta)genome data, aiding identification of natural product biosynthetic origins structures.
Actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70% the naturally derived antibiotics that currently in clinical use. In this study, we report on isolation Streptomyces sp. strains from Mediterranean sponges, their secondary metabolite production and screening anti-infective activities. Bioassay-guided purification yielded three previously known namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine butenolide. This...
Wnt proteins are secreted post-translationally modified that signal locally to regulate development and proliferation. The production of bioactive Wnts requires a number dedicated factors in the secreting cell whose coordinated functions not fully understood. A screen for small molecules identified inhibitors vacuolar acidification as potent secretion. Inhibition V-ATPase or disruption pH gradients by diverse drugs potently inhibited Wnt/β-catenin signaling both cultured human cells vivo,...
Natural products profoundly impact many research areas, including medicine, organic chemistry, and cell biology. However, discovery of new natural suffers from a lack high throughput analytical techniques capable identifying structural novelty in the face degree chemical redundancy. Methods to select bacterial strains for drug have historically been based on phenotypic qualities or genetic differences not laboratory production secondary metabolites. Therefore, untargeted LC/MS-based...
Bioassay-guided metabolomic analyses led to the characterization of four new 20-membered glycosylated polyketide macrolactams, macrotermycins A–D, from a termite-associated actinomycete, Amycolatopsis sp. M39. M39's sequenced genome revealed macrotermycin's putative biosynthetic gene cluster. Macrotermycins A and C had antibacterial activity against human-pathogenic Staphylococcus aureus and, greater ecological relevance, they also selective antifungal fungal parasite termite garden.
Advances in genomics and metabolomics have made clear recent years that microbial biosynthetic capacities on Earth far exceed previous expectations. This is attributable, part, to the realization most natural product (NP) producers harbor machineries not readily amenable classical laboratory fermentation conditions. Such "cryptic" or dormant gene clusters (BGCs) encode for a vast assortment of potentially new antibiotics and, as such, become extremely attractive targets activation under...
Abstract Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans , was discovered using LCMS‐based metabolomics to investigate marine‐invertebrate‐associated bacteria. A had highly unusual and unprecedented skeleton. Acquisition of 13 C– C gCOSY 15 N HMQC NMR data provided the direct carbon–carbon carbon–nitrogen connectivity, respectively. This approach represents first example determining connectivity for natural product. Using yeast chemical genomics, we...
Paclitaxel cytotoxicity in breast tumors depends on multipolar spindle maintenance and preexisting chromosomal instability.
There is a need for diverse molecular libraries phenotype-selective and high-throughput screening. To make marine natural products (MNPs) more amenable to newer screening paradigms shorten discovery time lines, we have created an MNP library characterized online using MS. test the potential of library, screened subset in screen identify compounds that inhibited growth BRCA2-deficient cells.
GilOII has been unambiguously identified as the key enzyme performing crucial C-C bond cleavage reaction responsible for unique rearrangement of a benz[a]anthracene skeleton to benzo[d]naphthopyranone backbone typical gilvocarcin-type natural anticancer antibiotics. Further investigations this led isolation hydroxyoxepinone intermediate, leading important conclusions regarding mechanism.
Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain associated with fungus-growing termites. The structures of 1 2 determined by 1D- 2D-NMR spectroscopy high-resolution mass spectrometry. Structural elucidation led to the re-examination structure originally proposed for vinylamycin (3). Based on comparison predicted experimental 1H 13C NMR chemical shifts, we propose that vinylamycin's be revised 3 4.
ABSTRACT Endocrocin is a simple anthraquinone frequently identified in extracts of numerous fungi. Several biosynthetic schemes for endocrocin synthesis have been hypothesized, but to date, no dedicated secondary metabolite gene cluster that produces this polyketide as its major has identified. Here we describe our and regulatory characterization the Aspergillus fumigatus . This first report species. The genes required production are regulated by global regulator metabolism, LaeA, encode an...
Drug resistant infectious diseases are quickly becoming a global health crisis. While Streptomyces spp. have been major source of antibiotics over the past 50 years, efficient methods needed to identify new and greatly improve rate discovery. LCMS-based metabolomics were applied analyze extracts Streptomyes Using this methodology, we discovered bottromycin D used whole genome sequencing determine its biosynthesis by ribosomal pathway.
A marine Verrucosispora sp. isolated from the sponge Chondrilla caribensis f. was found to produce thiocoraline, a potent cytotoxic compound. Five new analogs of thiocoraline were and represent first thiocoraline. 22′-Deoxythiocoraline (2), thiochondrilline C (5), 12′-sulfoxythiocoraline (6) demonstrated significant cytotoxicity against A549 human cancer cell line with EC50 values 0.13, 2.86, 1.26 μM, respectively. The provide insight into SAR biosynthesis DP4 probability method used analyze...
A marine Nocardia sp. isolated from the ascidian Trididemnum orbiculatum was found to produce five new lipopeptides, peptidolipins B–F (1–5), which show distinct similarities previously reported l-Val(6) analog of peptidolipin NA. Synthetic modification E (4) used determine location an olefin within lipid chain. The advanced Marfey's method absolute configurations amino acids. Peptidolipins B (1) and demonstrated moderate antibacterial activity against methicillin-resistant Staphylococcus...
Bacterial strains isolated from attine ants showed activity against the insect specialized fungal pathogen Escovopsis and also human protozoan parasite Leishmania donovani. The bioassay guided fractionation of extracts cultures Streptomyces sp. ICBG292, exoskeleton Cyphomyrmex workers, led to isolation Mer-A2026B (1), piericidin-A1 (2) nigericin (3). Nigericin (3) presented high intracellular amastigotes L. donovani (IC50 0.129 ± 0.008 μM). puniceus ICBG378, workers Acromyrmex rugosus...
The emergence of drug-resistant fungi has prompted an urgent threat alert from the US Centers for Disease Control (CDC). Biofilm assembly by these pathogens further impairs effective therapy. We recently identified antifungal, turbinmicin, that inhibits fungal vesicle-mediated trafficking pathway and demonstrates broad-spectrum activity against planktonically growing fungi. During biofilm growth, vesicles with unique features play a critical role in delivery extracellular matrix components....
The discovery of new natural products remains a cornerstone therapeutic innovation, and effective analytical tools for rapid dereplication can significantly accelerate this process. Using Isotopic Fine Structure (IFS) mass spectrometry, we rapidly identified three dimeric benzofluorene glycosides, lomaiviticins F–H (1–3), from marine-derived Micromonospora sp. bacterium. These compounds were isolated structurally elucidated through advanced spectroscopic techniques, including FT-ICR-MS NMR....