A5031625191- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Chemical synthesis and alkaloids
- Computational Drug Discovery Methods
- Microbial Fuel Cells and Bioremediation
- Electrochemical sensors and biosensors
- Microbial Metabolism and Applications
- Insect and Arachnid Ecology and Behavior
- Plant-Microbe Interactions and Immunity
- Electrochemical Analysis and Applications
- Insect symbiosis and bacterial influences
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- Synthetic Organic Chemistry Methods
- Algal biology and biofuel production
- Insect and Pesticide Research
- Antimicrobial Peptides and Activities
- Microbial Community Ecology and Physiology
- ATP Synthase and ATPases Research
- Phytochemistry and Biological Activities
- Bioactive Compounds and Antitumor Agents
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Biological Activity
- Bacterial biofilms and quorum sensing
- Advanced Synthetic Organic Chemistry
Virginia Tech
2020-2025
Harvard University
2015-2021
University of California, San Diego
2010-2021
Scripps Institution of Oceanography
2012-2021
University of South Florida
2012
Picking structures out of a lineup Pharmaceutical research relies critically on determining the correct numerous complex molecules. When well-ordered crystals are not available for x-ray analysis, nuclear magnetic resonance (NMR) spectroscopy is most common structure-elucidation method. However, sometimes it hard to distinguish isomers with similar spectra. Liu et al. showcase protocol that combines computer modeling anisotropic NMR data acquired using gel-aligned samples. Because its...
Microbes sense and respond to their environment with small molecules, discovering these molecules identifying functions informs chemistry, biology, medicine. As part of a study molecular exchanges between termite-associated actinobacteria pathogenic fungi, we uncovered remarkable fungal metabolite, homodimericin A, which is strongly upregulated by the bacterial metabolite bafilomycin C1. Homodimericin A hexacyclic polyketide carbon backbone containing eight contiguous stereogenic carbons in...
The rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated the search for new antibiotics. Many clinically used antibacterials were discovered through culturing a single microbial species under nutrient-rich conditions, but in environment, constantly encounter poor nutrient conditions and interact with neighboring species. In an effort to recapitulate this we generated nine-strain actinomycete community 16S rDNA sequencing deconvolute stochastic production antimicrobial...
A family of cancer cell cytotoxic cyclodepsipeptides, veraguamides A−C (1−3) and H−L (4−8), were isolated from a collection cf. Oscillatoria margaritifera obtained the Coiba National Park, Panama, as part Panama International Cooperative Biodiversity Group program. The planar structure veraguamide (1) was deduced by 2D NMR spectroscopy mass spectrometry, whereas structures 2−8 mainly determined combination 1H MS2/MS3 techniques. These new compounds are analogous to mollusk-derived...
Abstract Five lipopeptides of the lyngbyabellin structure class, four cyclic ( 1 – 3 and 5 ) one linear 4 ), were isolated from extracts two collections filamentous marine cyanobacteria obtained Palmyra Atoll in Central Pacific Ocean. Their planar structures absolute configurations elucidated through a combination spectroscopic chromatographic analyses as well chemical synthesis fragments. In addition to structural features typical lyngbyabellins, such thiazole rings chlorinated...
Some anaerobic bacteria use insoluble minerals as terminal electron acceptors and discovering the ways in which electrons move through membrane barrier to exterior acceptor forms an active field of research with implications for both bacterial physiology bioenergy. A previous study suggested that Shewanella oneidensis MR-1 utilizes a small, polar, redox molecule serves shuttle between acceptors, but itself has never been identified. Through isolation synthesis, we identify it ACNQ...
Fungus-growing ants engage in a multilateral symbiosis: they cultivate fungal garden as their primary food source and host symbiotic actinobacteria (Pseudonocardia spp.) that provide chemical defenses. The bacterial symbionts produce small specialized metabolites protect the from specific pathogens (Escovopsis spp.), return, are fed by ant hosts. Multiple studies on molecules underlying this system have led to discovery of large number structurally diverse antifungal molecules, but somewhat...
Biofilms commonly develop in immunocompromised patients, which leads to persistent infections that are difficult treat. In the biofilm state, bacteria protected against both antibiotics and host's immune system; currently, there no therapeutics target biofilms. this study, we screened a chemical fraction library representing natural product capacity of microbiota marine egg masses, namely, moon snail collars. This led identification active fractions targeting Pseudomonas aeruginosa...
The recent explosion in the described chemistry from Colobognatha, a millipede subterclass, has rekindled interest defensive secretions these ancient animals. Colobognatha are only millipedes that produce terpenoid alkaloids, and prior to 2020, studies into were limited single order, Polyzoniida. However, it become clear numerous species of order Platydesmida also structurally diverse alkaloids with potent biological activity. encompass multiple natural product scaffolds greater chemical...
Lactiplantibacillus plantarum is known to utilize exogenous small molecule quinone mediators perform extracellular electron transfer (EET), allowing it produce a detectable current in bioelectrochemical system (BES). Utilization of by L. requires type-II NADH dehydrogenase (Ndh2); however, structural variations the core 1,4-naphthoquinone EET have shown yield significantly different outputs. Herein, we assembled library 40 quinone-based probe important physicochemical properties and...
Abstract Lactiplantibacillus plantarum is known to utilize exogenous small molecule quinone mediators perform extracellular electron transfer (EET), allowing it produce a detectable current in bioelectrochemical system (BES). Utilization of by L. requires type‐II NADH dehydrogenase (Ndh2); however, structural variations the core 1,4‐naphthoquinone EET have shown yield significantly different outputs. Herein, we assembled library 40 quinone‐based probe important physicochemical properties and...
Bacterial symbionts frequently provide chemical defenses for their hosts, and such systems can discovery pathways to new antifungals structurally intriguing metabolites. This report describes a small family of naturally occurring molecules with chimeric structures mixed biosynthesis that features an unexpected but key nonenzymatic step. An insect-associated Pseudomonas protegens strain's activity in vivo murine candidiasis assay led the highly hydrogen-deficient Bioactivity- mass-guided...
Overexpression of the Pseudomonas virulence factor (pvf) biosynthetic operon led to identification a family pyrazine N-oxides (PNOs), including novel dihydropyrazine N,N′-dioxide (dPNO) metabolite. The nonribosomal peptide synthetase responsible for production (d)PNOs was characterized, and pathway proposed. This work highlights unique chemistry catalyzed by pvf-encoded enzymes sets stage bioactivity studies metabolites produced pathway.
Significance A number of plant-associated bacteria possess transcription factors homologous to LuxR that respond compounds found in plant tissue. These homologs are known regulate virulence or symbiosis. Although the first these proteins were described more than a decade ago, they remain unknown. Here we identify compound functions with PipR, plant-responsive homolog from tree root endopytic Pseudomonas isolate. The inducer is an ethanolamine derivative. Ethanolamine building block for...
Genome sequencing of microorganisms has revealed a greatly increased capacity for natural products biosynthesis than was previously recognized from compound isolation efforts alone. Hence, new methods are needed the discovery and description this hidden secondary metabolite potential. Here we show that provision heavy nitrogen 15N-nitrate to marine cyanobacterial cultures followed by single-filament MALDI analysis over period days highly effective in identifying product with an exceptionally...
Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving previously isolated or synthesized compounds largely completely untested. To address this issue, the Canvass library natural was assembled, in collaboration with academic industry researchers, quantitative high-throughput screening (qHTS) across a diverse set cell-based biochemical assays. Characterization...
Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion the oxidative phosphorylation system (OXPHOS). Idebenone menadione are redox-active molecules capable rescuing OXPHOS activity by engaging I-independent pathways entry, often referred as "complex bypass." In present study, created a cellular model deficiency using CRISPR genome editing knock out Ndufa9 mouse myoblasts, utilized cell line develop...
Methane-oxidizing bacteria, aerobes that utilize methane as their sole carbon and energy source, are being increasingly studied for environmentally significant ability to remove from the atmosphere. Their genomes indicate they also have a robust unusual secondary metabolism. Bioinformatic analysis of Methylobacter tundripaludum genome identified biosynthetic gene clusters several intriguing metabolites, this report discloses structural genetic characterization tundrenone, one these...
Previous studies identified an adamantane dipeptide piperazine 3.47 that inhibits Ebola virus (EBOV) infection by targeting the essential receptor Niemann–Pick C1 (NPC1). The physicochemical properties of limit its potential for testing in vivo. Optimization improving potency, reducing hydrophobicity, and replacing labile moieties derivatives with improved vitro ADME are also highly active against EBOV infection, including when tested presence 50% normal human serum (NHS). In addition, 3A4...
Herein is a report on the molecular exchange occurring between multilateral symbiosis partners—a tit-for-tat that led to characterization of two new metabolites, conocandin B (fungal-derived) and dentigerumycin F (bacterial-derived). The structures were determined by NMR, mass spectrometry, genomic analysis, chemical derivatizations. Conocandin exhibits antimicrobial activity against both bacterial symbionts fungus-growing ant human pathogenic strains selectively inhibiting FabH, thus...
While quinones are essential for respiratory microorganisms, their importance microbes that rely on fermentation metabolism is not understood. This gap in knowledge hinders our understanding of anaerobic microbial habitats, such mammalian digestive tracts and fermented foods. We show
Bioassay-guided fractionation of a collection Moorea bouillonii from Papua New Guinea led to the isolation new alkyl amide, mooreamide A (1), along with cytotoxic apratoxins A-C and E. The planar structure 1 was elucidated by NMR spectroscopy mass spectrometry analysis. Structural homology between endogenous cannabinoid ligands, anandamide, 2-arachidonoyl glycerol inspired its evaluation against neuroreceptors CB(1) CB(2). Mooreamide found possess relatively potent selective ligand binding...
Two new marine cyanobacterial natural products, parguerene (1) and precarriebowmide (2), were isolated from a collection of Moorea producens obtained La Parguera, Puerto Rico. The planar structures both deduced by 2D NMR spectroscopy mass spectrometry. Parguerene is modified acyl amide with some structural similarity to the bacterial metabolite stipiamide (3), whereas lipopeptide represents minor modification compared two other known metabolites, carriebowmide (4) sulfone (5). identification...