A5108055597- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- Chemical Synthesis and Analysis
- Microbial Metabolism and Applications
- Marine Sponges and Natural Products
- Carbohydrate Chemistry and Synthesis
- Sulfur-Based Synthesis Techniques
- Acne and Rosacea Treatments and Effects
- Click Chemistry and Applications
- Fungal Biology and Applications
- Glycosylation and Glycoproteins Research
- Synthetic Organic Chemistry Methods
- Phytochemistry and Bioactive Compounds
- Antimicrobial Peptides and Activities
- Monoclonal and Polyclonal Antibodies Research
- Catalytic C–H Functionalization Methods
- Mass Spectrometry Techniques and Applications
- Chemical Reactions and Isotopes
- Retinoids in leukemia and cellular processes
- Studies on Chitinases and Chitosanases
- Plant-Microbe Interactions and Immunity
University of Florida
2023-2024
The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
2023-2024
Scripps (United States)
2024
Emory University
2023
Scripps Research Institute
2019-2021
Actinobacteria, the bacterial phylum most renowned for natural product discovery, has been established as a valuable source drug discovery and biotechnology but is underrepresented within accessible genome strain collections. Herein, we introduce Natural Products Discovery Center (NPDC), featuring 122,449 strains assembled over eight decades, genomes of first 8490 NPDC (7142 Actinobacteria), online Portal making both publicly available. A comparative survey RefSeq Actinobacteria highlights...
Nature forms S-S bonds by oxidizing two sulfhydryl groups, and no enzyme installing an intact hydropersulfide (-SSH) group into a natural product has been identified to date. The leinamycin (LNM) family of products features bonds, previously we reported SH domain (LnmJ-SH) within the LNM hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line as cysteine lyase that plays role in sulfur incorporation. Here report characterization S-adenosyl methionine...
Development of efficient protocols for introducing handles into natural products and pharmaceutical agents that are suitable bioconjugation is a compelling research objective. One attractive option would involve chemical tagging through late-stage C–H functionalization, but such strategies uncommon. The primary challenge lies in the lack catalyst systems can chemo- site-selectively cleave relatively inert bonds. In this study, we demonstrate bioactive N-alkylamine-based other small-molecule...
Antibody–drug conjugates (ADCs) are cancer chemotherapeutics that utilize a monoclonal antibody (mAb)-based delivery system, cytotoxic payload, and chemical linker. ADC payloads must be strategically functionalized to allow linker attachment without perturbing the potency required for efficacy. We previously developed biocatalytic system precise functionalization of tiancimycin (TNM)-based payloads. The TNMs anthraquinone-fused enediynes (AFEs) have yet translated into clinic. Herein, we...
Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) 16 other analogs as potential anti-C. acnes compounds found that CD437 displayed highest antimicrobial with an MIC against C. (ATCC 6919 HM-513) 1 μg/mL. demonstrated MBC 2 μg/mL compared to up 64 for adapalene tetracycline, which are commonly used clinically...
Structural and functional studies of the carminomycin 4-O-methyltransferase DnrK are described, with an emphasis on interrogating acceptor substrate scope DnrK. Specifically, evaluation 100 structurally functionally diverse natural products product mimetics revealed array pharmacophores as productive substrates. Representative newly identified substrates from this study included anthracyclines, angucyclines, anthraquinone-fused enediynes, flavonoids, pyranonaphthoquinones, polyketides. The...
Iso-Migrastatin (iso-MGS) and lactimidomycin (LTM) are glutarimide-containing polyketide natural products (NPs) that biosynthesized by homologous acyltransferase (AT)-less type I synthase (PKS) assembly lines. The biological activities of iso-MGS LTM have inspired numerous efforts to generate analogues via genetic manipulation their biosynthetic machinery in both native producers model heterologous hosts. A detailed understanding the MGS AT-less PKSs would serve inspire future engineering...
Polyketide synthases (PKSs) are renowned for the structural diversity of polyketide natural products they produce, but sulfur-containing functionalities rarely installed by PKSs. We previously characterized thiocysteine lyase (SH) domains involved in biosynthesis leinamycin (LNM) family products, exemplified LnmJ-SH and guangnanmycin (GnmT-SH). Here we report a detailed investigation into PLP-dependent reaction catalyzed SH domains, guided 1.8 Å resolution crystal structure GnmT-SH. A series...