A5029255466- Microbial Natural Products and Biosynthesis
- Plant biochemistry and biosynthesis
- Carbohydrate Chemistry and Synthesis
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Phytochemical compounds biological activities
- Cancer therapeutics and mechanisms
- Enzyme Production and Characterization
- Synthetic Organic Chemistry Methods
- Bioactive Compounds and Antitumor Agents
- Biochemical and Structural Characterization
- Alkaloids: synthesis and pharmacology
- Protein Hydrolysis and Bioactive Peptides
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Traditional and Medicinal Uses of Annonaceae
- Heat shock proteins research
- Insect symbiosis and bacterial influences
- Antimicrobial Peptides and Activities
- Seaweed-derived Bioactive Compounds
- Microbial Community Ecology and Physiology
- 14-3-3 protein interactions
- Glycosylation and Glycoproteins Research
- Synthesis of Indole Derivatives
- Insect and Arachnid Ecology and Behavior
Chapman University
2018-2024
University of Kentucky
2013-2018
University of Utah
2015
Oregon Health & Science University
2009-2013
The relationship between tunicates and the uncultivated cyanobacterium Prochloron didemni has long provided a model symbiosis. P. is required for survival of animals such as Lissoclinum patella also makes secondary metabolites pharmaceutical interest. Here, we present metagenomes, chemistry, microbiomes four related L. tunicate samples from wide geographical range tropical Pacific. remarkably similar genomes are most complex so far assembled organisms. Although not been stably cultivated...
Shipworms are marine wood-boring bivalve mollusks (family Teredinidae) that harbor a community of closely related Gammaproteobacteria as intracellular endosymbionts in their gills. These symbionts have been proposed to assist the shipworm host cellulose digestion and shown play role nitrogen fixation. The genome one strain Teredinibacter turnerae , first symbiont be cultivated, was sequenced, revealing potential rich source polyketides nonribosomal peptides. Bioassay-guided fractionation led...
Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in gills wood-boring bivalves family Teredinidae (shipworms). This species sole cultivated member endosymbiotic consortium thought to provide host with enzymes, including cellulases and nitrogenase, critical for digestion wood supplementation host's nitrogen-deficient diet. closely related free-living polysaccharide degrading...
Appalachian active coal fire sites were selected for the isolation of bacterial strains belonging to class actinobacteria. A comparison high-resolution electrospray ionization mass spectrometry (HRESIMS) and ultraviolet (UV) absorption profiles from isolate extracts natural product databases suggested Streptomyces sp. RM-4-15 produce unique metabolites. Four new pyranonaphthoquinones, frenolicins C–F (1–4), along with three known analogues, frenolicin (6), B (7), UCF76-A (8), isolated...
The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B C (4, 5), carboxamides 6–8] 11 previously reported (1, 3, 9–12a, 14–18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis comprehensive 1D 2D NMR mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, 12a,b. Complete assignments known lenoremycin (9) sodium salt (10) also provided first time. Comparative analysis...
Terfestatins B (1) and C (2), new p-terphenyls bearing a novel unsaturated hexuronic acid (4-deoxy-α-l-threo-hex-4-enopyranuronate), unique β-d-glycosyl ester of 5-isoprenylindole-3-carboxylate (3) the same rare sugar, two hygromycin precursors, were characterized as metabolites coal mine fire isolate Streptomyces sp. RM-5–8. EtOH damage neuroprotection assays using rat hippocampal-derived primary cell cultures with 1, 2, 3 echoside (a terfestatin C-3′-β-d-glucuronide from RM-5–8) revealed 1...
Actinomadura melliaura ATCC 39691, a strain isolated from soil sample collected in Bristol Cove, California, is known producer of the disaccharide-substituted AT2433 indolocarbazoles (6–9). Reinvestigation this using new media conditions led to >40-fold improvement production previously reported metabolites and isolation structure elucidation four analogues, AT2433-A3, A4, A5, B3 (1–4). The availability broader set compounds enabled subsequent small antibacterial/fungal/cancer SAR study that...
Bacterial strains belonging to the class actinomycetes were isolated from soil near a thermal vent of Ruth Mullins coal fire (Appalachian Mountains eastern Kentucky). High-resolution electrospray ionization mass spectrometry and ultraviolet absorption profiles metabolites one isolates (Streptomyces sp. RM-7-15) revealed presence unique set ultimately determined be herbimycins D–F (1–3). In addition, herbimycin A (4), dihydroherbimycin (TAN 420E) (7), structurally distinct antibiotic...
Abstract Four cyclopentenone‐containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including linear mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD‐23‐14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models Gdm D confirmed that mccrearamycin cyclopentenone derives benzilic rearrangement 19‐hydroxy Gdm, thereby provides a...
Four new Y-type actinomycin analogues named Y6–Y9 (1–4) were isolated and characterized from the scale-up fermentation of Streptomyces sp. strain Gö-GS12, as well Zp (5), which was, for first time, a natural product. Structures compounds elucidated by cumulative analyses NMR spectroscopy HRMS. The 4-hydroxythreonine on β-ring 1 uniquely undergoes both rearrangement 2-fold acyl shift an additional ring closure with amino group phenoxazinone chromophore, α-rings 4 5 contain rare 5-methyl...
The structures of 12 new "enantiomeric"-like abyssomicin metabolites (abyssomicins M–X) from Streptomyces sp. LC-6-2 are reported. Of this set, the W (11) contains an unprecedented 8/6/6/6 tetracyclic core, while bicyclic X (12) represents first reported naturally occurring linear spirotetronate. Metabolite were determined based on spectroscopic data and X-ray crystallography, genome sequencing also revealed corresponding putative biosynthetic gene cluster.
The structures and bioactivities of three unprecedented fused 5-hydroxyquinoxaline/alpha-keto acid amino metabolites (baraphenazines A–C, 1–3), two unique diastaphenazine-type D E, 4 5) new phenazinolin-type F G, 6 7) from the Himalayan isolate Streptomyces sp. PU-10A are reported. This study highlights first reported bacterial strain capable producing diastaphenazine-type, phenazinolin-type, izumiphenazine A-type presents a opportunity for future biosynthetic interrogation late-stage...
Site-selective modification of complex peptides and the functionalization their C–H bonds hold great promise for expanding use in therapeutics biomedical research. Herein, we leverage power late-stage chemoenzymatic catalysis using an indole prenyltransferase (IPT) enzyme alkyl diphosphates to specifically modify ring tryptophan clinically relevant peptides. Furthermore, installed handle enables bioorthogonal click chemistry through inverse electron-demand Diels–Alder (IEDDA) reaction with a...
The isolation and structural elucidation of a new tetracyclic polyketide (ruthmycin) from Streptomyces sp. RM-4-15, bacteria isolated near thermal vents the Ruth Mullins underground coal mine fire in eastern Kentucky, is reported. In comparison to well-established frenolicin core scaffold, ruthmycin possesses an unprecedented signature C3 bridge corresponding fused six member ring. Preliminary vitro antibacterial, anticancer, antifungal assays revealed display moderate activity.
Calicheamicin γ1I (1) is an enediyne antitumor compound produced by Micromonospora echinospora spp. calichensis, and its biosynthetic gene cluster has been previously reported. Despite extensive analysis biochemical study, several genes in the of 1 remain functionally unassigned. Using a structural genomics approach characterization, two proteins encoded from assigned as "unknowns", CalU16 CalU19, were characterized. Structure revealed that they possess STeroidogenic Acute Regulatory protein...
The isolation and structure elucidation of four new naturally occurring amino-nucleoside [puromycins B–E (1–4)] metabolites from a Himalayan isolate (Streptomyces sp. PU-14-G, isolated the Bara Gali region northern Pakistan) is reported. Consistent with prior reports, comparative antimicrobial assays revealed need for free 2″-amine anti-Gram-positive bacteria antimycobacterial activity. Similarly, cancer cell line cytotoxicity highlighted importance puromycin-free impact 3′-nucleoside...
We report the production, isolation and structure elucidation of sesquiterpene isopterocarpolone from an Appalachian isolate Streptomyces species RM-14-6. While was previously put forth as a putative plant metabolite, this study highlights first native bacterial production full characterisation using 1D 2D NMR spectroscopy HR-ESI mass spectrometry. Considering biosynthesis closely related metabolites (geosmin or 5-epiaristolochene), also suggests potential participation one more unique...
Abstract Daptomycin (DAP) is a calcium (Ca 2+ )‐dependent FDA‐approved antibiotic drug for the treatment of Gram‐positive infections. It possesses complex pharmacophore hampering derivatization and/or synthesis analogues. To mimic Ca ‐binding effect, we used chemoenzymatic approach to modify tryptophan (Trp) residue DAP and synthesize kinetically characterized structurally elucidated regiospecific Trp‐modified We demonstrated that modified DAPs are several times more active than parent...
The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification leads to changes in their biological properties. Here, the synthesis two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method demonstrated which uses a promiscuous indole prenyltransferase enzyme install dual moiety directly on ring peptides. This first report modifications this group.
We report the isolation and characterization of three new nybomycins (nybomycins B-D,