A5030493200- Microbial Natural Products and Biosynthesis
- Fungal Biology and Applications
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Plant biochemistry and biosynthesis
- Chemical Synthesis and Analysis
- Marine Sponges and Natural Products
- Natural product bioactivities and synthesis
- Coral and Marine Ecosystems Studies
- Synthetic Organic Chemistry Methods
- Synthesis and Catalytic Reactions
- Fungal and yeast genetics research
- Genomics and Phylogenetic Studies
- Protein purification and stability
- Protist diversity and phylogeny
- Aquaculture disease management and microbiota
- Mass Spectrometry Techniques and Applications
- Radical Photochemical Reactions
- Catalytic C–H Functionalization Methods
- Analytical Chemistry and Chromatography
- Plant Pathogens and Fungal Diseases
- Mycotoxins in Agriculture and Food
- Chemical synthesis and alkaloids
- Parkinson's Disease Mechanisms and Treatments
- Phytochemistry and Biological Activities
Loxo Oncology at Lilly (United States)
2022-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2020-2023
Oregon State University
2016-2021
Shuffling nitrogen with a light push Manipulation of carbon–nitrogen rings is integral to the synthesis numerous pharmaceutical and agrochemical compounds. Jurczyk et al . report that photoexcitation carbonyl-substituted cyclic amines can shift from inside outside ring framework. The reaction appears proceed through 1,5-hydrogen electronically excited carbonyl, which sets in motion subsequent carbon–carbon bonding rearrangements. Several oxygen sulfur heterocycles were applicable as well....
Saturated cyclic amines (aza-cycles) are ubiquitous structural motifs found in pharmaceuticals, agrochemicals, and bioactive natural products. Given their importance, methods that directly functionalize aza-cycles high demand. Herein, we disclose a fundamentally different approach to functionalizing which relies on C–C cleavage attendant cross-coupling. The initial functionalization step is the generation of underexplored N-fused bicyclo α-hydroxy-β-lactams under mild, visible light...
A new bicyclic diterpenoid, benditerpenoic acid, was isolated from soil-dwelling Streptomyces sp. (CL12-4). We sequenced the bacterial genome, identified responsible biosynthetic gene cluster, verified function of terpene synthase, and heterologously produced core diterpene. Comparative bioinformatics indicated this strain is phylogenetically unique possesses nine synthases. The absolute configurations trans-fused bicyclo[8.4.0]tetradecanes were achieved by extensive spectroscopic analyses,...
Filamentous fungi produce a vast number of asexual spores that act as efficient propagules. Due to their infectious and/or allergenic nature, fungal affect our daily life. Aspergillus species called conidia; formation involves morphological development and metabolic changes, the associated regulatory systems are coordinated by multiple transcription factors (TFs).
The leucine-rich repeat kinase 2 (LRRK2) protein has been genetically and functionally linked to Parkinson's disease (PD), a disabling progressive neurodegenerative disorder whose current therapies are limited in scope efficacy. In this report, we describe rigorous hit-to-lead optimization campaign supported by structural enablement, which culminated the discovery of brain-penetrant, candidate-quality molecules as represented compounds 22 24. These exhibit remarkable selectivity against...
The genetically encoded, small-molecule chemical diversity of filamentous fungi is still largely unexplored and represents an attractive source for the discovery new compounds. Here we report production chlorinated bianthrones from coculture two different developmental stages, or morphs, a marine alga-derived Aspergillus alliaceus (teleomorph: Petromyces alliaceus) strain. vegetative stage (asexual morph) can be separated morph that switched to sexual development (sclerotial morph); both...
Mutualisms between cnidarian hosts and dinoflagellate endosymbionts are foundational to coral reef ecosystems. These symbioses often re-established every generation with high specificity, but gaps remain in our understanding of the cellular mechanisms that control symbiont recognition uptake dynamics. Here, we tested whether differences glycan profiles among different species account for rates at which they initially colonize aposymbiotic polyps model sea anemone Aiptasia (Exaiptasia...
Abstract A comparative metabolomic study of a marine derived fungus ( Aspergillus terreus ) grown under various culture conditions is presented. The was in eleven different using solid agar, broth cultures, or grain based media (OSMAC). Multivariate analysis LC/MS data from the organic extracts revealed drastic differences metabolic profiles and guided our subsequent isolation efforts. compound 7‐desmethylcitreoviridin isolated identified, fully described for first time. In addition, 16...
The diversity of genetically encoded small molecules produced by filamentous fungi remains largely unexplored, which makes these an attractive source for the discovery new compounds. However, accessing their full chemical repertoire under common laboratory culture conditions is a challenge. Epigenetic manipulation gene expression has become well-established tool overcoming this obstacle. Here, we report that perturbation endophytic ascomycete Chalara sp. 6661, producer isofusidienol class...
Fungal natural products have inspired and enabled countless modern therapeutics. During a survey of the secondary metabolites endophytic fungi, we found that Aspergillus porosus produces new polyketides with interesting structural features named porosuphenols A–D (1, 2, 3a, 3b). The elucidation these was performed 1D 2D NMR techniques, Mosher ester analysis, J-based conformational isotope exchange studies. absolute configuration compounds determined using typical approaches including...
The construction of complex aza-cycles is interest to drug discovery due the prevalence nitrogen-containing heterocycles in pharmaceutical agents. Herein we report an intramolecular C-H amination approach afford value-added and complexity-enriched bridged bicyclic amines. Guided by density functional theory nuclear magnetic resonance investigations, determined unique roles light heat activation bicyclization mechanism. We applied both a synergistic fashion, achieving gram-scale aza-cycle synthesis.
An enantio- and diastereoselective Rh-catalyzed conjugate addition reaction for the synthesis of proline analogues is reported. A high-throughput experimentation campaign was used to identify an efficient chiral catalyst which able afford desired products in high yield with levels diastereo- enantioselectivity. This method a range 3-substituted derivatives from readily available dehydroproline electrophiles boronic acid nucleophiles.
Comprehensive synthetic strategies afforded a diverse set of structurally unique bicyclic proline-containing arginase inhibitors with high degree three-dimensionality. The analogs that favored the Cγ-exo conformation proline improved potency over initial lead. novel reported here not only enable access to previously unknown stereochemically complex derivatives but also provide foundation for future synthesis analogs, which incorporate inherent three-dimensional character into building...
The saprotrophic filamentous fungus Myrothecium inundatum represents a chemically underexplored ascomycete with high number of putative biosynthetic gene clusters in its genome. Here, we present new linear lipopeptides from nongenetic activation experiments using nutrient and salt variations. Metabolomics studies revealed four myropeptins, structural analyses by NMR, HRMS, Marfey's analysis, ECD assessment for their helical properties established absolute configuration. A myropeptin cluster...
Recent technological and synthetic advances have led to a resurgence in the exploration of peptides as potential therapeutics. Understanding peptide conformation both free protein-bound states remains one most critical areas for successful development drugs. In this study it was demonstrated that combination Size-Exclusion Chromatography with Hydrogen-Deuterium Exchange Mass Spectrometry (SEC-HDX-MS) Circular Dichroism Spectroscopy (CD) can be used guide selection further NMR analysis....
Recent advances in the field of cancer biology have accelerated discovery and development novel biopharmaceuticals. At forefront these drug efforts are high-throughput screening, compressed timelines, limited sample quantities, all characteristic space. To meet program targets, large numbers protein variants must be produced, screened, characterized, presenting a daunting analytical challenge. Additionally, higher-order structure is paramount for function monitored as critical quality...
Abstract From arid, high desert soil samples collected near Bend, Oregon, 19 unique bacteria were isolated. Each strain was identified by 16S rRNA gene sequencing, and their organic extracts tested for antibacterial antiproliferative activities. Noteworthy, six (30 %) exhibited strong inhibition resulting in less than 50 % cell proliferation more one cancer model, at 10 μg/mL. Principal component analysis (PCA) of LC/MS data revealed drastic differences the metabolic profiles found these...
Abstract Ein neues bicyclisches Diterpenoid, Benditerpensäure, wurde aus einem im Erdreich vorkommenden Streptomyceten‐Stamm (CL12‐4) isoliert. Wir sequenzierten das Bakteriengenom, identifizierten den verantwortlichen Biosynthesegencluster, verifizierten die Funktion der Terpensynthase und produzierten heterolog Diterpenoid‐Grundgerüst. Vergleichende Bioinformatik zeigte, dass dieser phylogenetisch einzigartig ist neun Terpensynthasen besitzt. Die absoluten Konfigurationen neuen trans...
The plant endophyte