A5089981334- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Plant biochemistry and biosynthesis
- Chemical Synthesis and Analysis
- Antibiotic Resistance in Bacteria
- Fungal Biology and Applications
- Carbohydrate Chemistry and Synthesis
- Enzyme Structure and Function
- Genomics and Phylogenetic Studies
- Natural product bioactivities and synthesis
- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- Enzyme Production and Characterization
- Metabolism and Genetic Disorders
- Catalytic C–H Functionalization Methods
- Microscopic Colitis
- Chemical synthesis and alkaloids
- Synthesis and Catalytic Reactions
- Bioactive Compounds and Antitumor Agents
- Plant-Microbe Interactions and Immunity
- Antibiotic Use and Resistance
- DNA Repair Mechanisms
- Click Chemistry and Applications
- Immune Response and Inflammation
- Radical Photochemical Reactions
Kitasato University
2022-2025
Kitasato Institute Hospital
2023-2024
The University of Tokyo
2018-2022
Benzastatins have unique structures probably derived from geranylated p-aminobenzoic acids. The indoline and tetrahydroquinoline scaffolds are presumably formed by cyclization of the geranyl moiety, but mechanism was unknown. We studied benzastatin biosynthetic gene cluster Streptomyces sp. RI18; functions six enzymes encoded it were analyzed disruption in a heterologous host vitro enzyme assays. propose pathway for benzastatins which cytochrome P450 (BezE) is responsible...
Macrocyclic peptides, including depsipeptides, are an emerging new modality in drug discovery research. Tetraselide, antifungal cyclic peptide isolated from a marine-derived filamentous fungus, possesses unique amphiphilic structural feature consisting of five consecutive β-hydroxy-amino acid residues and fatty moieties. Because the structure elucidation naturally occurring product left six stereocenters ambiguous, we implemented bioinformatic analyses, chemical degradation studies chiral...
Macrocyclic peptides and depsipeptides are the emerging class of a new modality in drug discovery research. Tetraselide, an antifungal cyclic peptide isolated from marine-derived filamentous fungus, possesses unique amphiphilic structural feature that represents five consecutive β-hydroxy-amino acid fatty moieties. Because structure elucidation naturally occurring product left six stereocenters ambiguous, we implemented bioinformatic analyses, chemical degradation study chiral pool fragment...
Abstract Prenyl pyrophosphate methyltransferases enhance the structural diversity of terpenoids. However, molecular basis their catalytic mechanisms is poorly understood. In this study, using multiple strategies, we characterized a geranyl (GPP) C6‐methyltransferase, BezA. Biochemical analysis revealed that BezA requires Mg 2+ and solely methylates GPP. The crystal structures its complex with S ‐adenosyl homocysteine were solved at 2.10 2.56 Å, respectively. Further analyses site‐directed...
Macrocyclic peptides and depsipeptides are the emerging class of a new modality in drug discovery research. Tetraselide, an antifungal cyclic peptide isolated from marine-derived filamentous fungus, possesses unique amphiphilic structural feature that represents five consecutive β-hydroxy-amino acid fatty moieties. Because structure elucidation naturally occurring product left six stereocenters ambiguous, we implemented bioinformatic analyses, chemical degradation study chiral pool fragment...
Indolizidine alkaloids, which have versatile bioactivities, are produced by various organisms. Although the biosynthesis of some indolizidine alkaloids has been studied, enzymatic machinery for their in Streptomyces remains elusive. Here, we report identification and analysis biosynthetic gene cluster iminimycin, an alkaloid with a 6-5-3 tricyclic system containing iminium cation from griseus. The 22 genes, including four genes encoding polyketide synthases (PKSs), consist eight modules...
Tetronomycin (1), first isolated from a cultured broth of Streptomyces sp. by Juslen et al. in 1974, is polycyclic polyether compound. However, the biological activity 1 has not been thoroughly examined. In this study, we found that exhibits more potent antibacterial than two well-known drugs (vancomycin and linezolid) effective against several drug-resistant clinical isolates including methicillin-resistant Staphylococcus aureus vancomycin-resistant Enterococci. Furthermore, reassigned 13C...
Actinomycetes, rich in biosynthetic gene clusters (BGCs), are important sources of natural products (NPs). However, the rate discovering novel NPs from actinomycetes has declined, indicating need for a new strategy to obtain NPs. Herein, we present efficient discovery First, performed comprehensive analysis BGCs actinomycetes, evaluating average number and types per genus identify prolific NP producers. Our revealed that certain strains, such as those family Pseudonocardiaceae, possess...
Vancomycin is a potent and broad-spectrum antibiotic that binds to the d-Ala-d-Ala moiety of growing bacterial cell wall kills bacteria. This fascinating binding model prompted us design synthesize silica gels for establishment new physicochemical (PC) screening method. In this report, we confirmed vancomycin gel can be eluted with MeOH containing 50 mM TFA. Finally, enables purify from culture broth vancomycin-producing strain, Amycolatopsis orientalis.
We discovered a new tetronomycin analog, C-32-OH (2) from the Streptomyces sp. K20-0247 strain, which produces (1). After NMR analysis of 2, we determined planar structure. Futhermore, absolute stereochemistry 2 was deduced based on biosynthetic pathway 1 in strain and comparison experimental electronic circular dichroism (ECD) results with 2. While exihibits potent antibacterial activity aganist Gram-positive baceria including vancomycin-intermediate Staphylococcus aureus (VISA) strains...
Three new antiplasmodial compounds, named akedanones A (1), B (2), and C (3), were discovered from the cultured material of Streptomyces sp. K20-0187 isolated a soil sample collected at Takeda, Kofu, Yamanashi prefecture in Japan. The structures compounds 1–3 elucidated as 2,3-dihydronaphthoquinones having prenyl reverse groups by mass spectrometry nuclear magnetic resonance analyses. Compound 1 known furanonaphthoquinone I (4) showed potent vitro activity against chloroquine-sensitive...
Utilizing a binding mode-based physicochemical screening method using d-Ala-d-Ala silica gel, two new macrolactams, named banglactams A (1) and B (2), were discovered from the culture broth of Nonomuraea bangladeshensis K18–0086. In course our investigation, we found that gel precisely differentiated chemical structures separated them. However, not able to obtain enough 1 elucidate structure due its instability insolubility. To overcome this challenge, chemically modified improve solubility,...
In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated antifungal active Aspergillus burnettii. However, activity 1 has been revealed in only one fungal species, and mechanism action remains unknown. After validation mitochondrial...
Abstract Prenyl pyrophosphate methyltransferases enhance the structural diversity of terpenoids. However, molecular basis their catalytic mechanisms is poorly understood. In this study, using multiple strategies, we characterized a geranyl (GPP) C6‐methyltransferase, BezA. Biochemical analysis revealed that BezA requires Mg 2+ and solely methylates GPP. The crystal structures its complex with S ‐adenosyl homocysteine were solved at 2.10 2.56 Å, respectively. Further analyses site‐directed...
Luminamicin (1) isolated in 1985, is a macrodiolide compound exhibiting selective antibacterial activity against anaerobes. However, the of 1 was not fully examined. In this research, re-evaluation revealed that narrow spectrum and potent antibiotic againstClostridioides difficile(C. difficile) effective fidaxomicin resistantC. difficilestrain. This prompted us to obtain luminamicin difficilestrains for determination molecular target inC. difficile. Sequence analysis 1-resistantC....
Biosynthesis of cyclic structures natural products is important for generating their structural diversity. In some cases, these are responsible bioactivities (e.g., a β-lactam ring in antibiotics and an aziridine antitumor antibiotics). Therefore, cyclization reaction among the most steps biosynthesis products. steps, chemical reactions organic synthesis often used synthesizing structures. For example, Diels-Alder to biosynthesize decaline structure mevastatin lovastatin, which known HMG-CoA...
Terpenoids are the largest class of natural products and derived from C5 isoprene units. Recent discoveries modification enzymes in native units before cyclization or transfer reactions have revealed that with additional carbon atoms also used to produce terpenoids. These reports indicate utilization these is useful for enzymatic production non-natural In this study, we attempted methylgeranyl polyphenols, which not observed nature, by combining a geranyl pyrophosphate C6 methyltransferase,...