- Plant biochemistry and biosynthesis
- Microbial Natural Products and Biosynthesis
- Retinal Development and Disorders
- Molecular Biology Techniques and Applications
- Forensic and Genetic Research
- Neuroscience and Neuropharmacology Research
- Retinal Diseases and Treatments
- Natural product bioactivities and synthesis
- Ion channel regulation and function
- Metabolomics and Mass Spectrometry Studies
- Genomics and Phylogenetic Studies
- DNA and Nucleic Acid Chemistry
- Glaucoma and retinal disorders
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Genetic diversity and population structure
- RNA and protein synthesis mechanisms
- Synthetic Organic Chemistry Methods
- Photosynthetic Processes and Mechanisms
- Neural dynamics and brain function
- Liver physiology and pathology
- Probiotics and Fermented Foods
- Retinal and Optic Conditions
- Fermentation and Sensory Analysis
- RNA regulation and disease
University of Yamanashi
2001-2025
The University of Tokyo
2015-2025
Japan Science and Technology Agency
2022-2025
Takeda (Japan)
2021-2025
Keio University
2008-2024
Fukuoka Institute of Technology
2024
Tokyo Medical and Dental University
2024
San Francisco VA Medical Center
2024
University of California, San Francisco
2024
Jichi Medical University
2024
The pristine sample from the near-Earth carbonaceous asteroid (162173) Ryugu collected by Hayabusa2 spacecraft enabled us to analyze extraterrestrial material without uncontrolled exposure Earth's atmosphere and biosphere. initial analysis team for soluble organic matter reported detection of wide variety molecules including racemic amino acids in samples. Here we report uracil, one four nucleobases ribonucleic acid, aqueous extracts In addition, nicotinic acid (niacin, a B3 vitamer), its...
Abstract The sequencing of the 12 genomes members genus Drosophila was taken as an opportunity to reevaluate genetic and physical maps for 11 species, in part aid mapping assembled scaffolds. Here, we present overview importance cytogenetic biology concepts chromosomal evolution. Physical markers were used anchor genome assembly scaffolds polytene each species. In addition, a computational approach smaller on basis analysis syntenic blocks. We map data from sequenced non-Drosophila...
Metabolomics is an emerging technology that reveals homeostatic imbalances in biological systems. Global determination of metabolite concentrations body fluid and tissues provides novel anatomical aspects pathological conditions cannot be obtained from target-specific measurements. Here, we characterised metabolic imbalance Watanabe heritable hyperlipidaemic rabbits as a model hypercholesterolaemia. Using mass spectrometry-based system, measured total 335 metabolites plasma (liver, aorta,...
Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics normal tissues surgically resected pairwise from nine lung seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels enzymes involved in central carbon metabolism were also quantified. Metabolomic...
Principal component analysis (PCA) has been widely used to visualize high-dimensional metabolomic data in a two- or three-dimensional subspace. In metabolomics, some metabolites (e.g., the top 10 metabolites) have subjectively selected when using factor loading PCA, and biological inferences are made for these metabolites. However, this approach may lead biased because not objectively with statistical criteria. We propose procedure that selects hypothesis testing of PCA makes about...
Samples from the carbonaceous asteroid (162173) Ryugu provide information on chemical evolution of organic molecules in early solar system. Here we show element partitioning major component ions by sequential extractions salts, carbonates, and phyllosilicate-bearing fractions to reveal primordial brine composition primitive asteroid. Sodium is dominant electrolyte salt fraction extract. Anions NH4+ are more abundant than carbonate phyllosilicate fractions, with molar concentrations order...
The structure of an Ag(I) -mediated cytosine-cytosine base pair, C-Ag(I) -C, was determined with NMR spectroscopy in solution. observation 1-bond (15) N-(109) Ag J-coupling ((1) J((15) N,(109) Ag): 83 and 84 Hz) recorded within the -C pair evidenced N3-Ag(I) -N3 linkage -C. triplet resonances N4 atoms demonstrated that each exocyclic atom exists as amino group (-NH2 ), any isomerization and/or N4-Ag(I) bonding can be excluded. 3D -DNA complex NOEs classified a B-form conformation notable...
We investigated the accuracy and reproducibility of relative flow volume (RFV), a novel index blood in human retina derived from laser speckle flowgraphy (LSFG).Pre- postbranch retinal RFV measurements were compared 34 venous bifurcations healthy volunteers (mean age, 49.0 ± 14.8 years) to determine RFV. Next, coefficient variation (COV) was determined for 30 temporal arteries second group 18 30.3 7.7 years). Finally, Doppler velocimetry (LDV) data obtained same study population vessels.A...
Abstract Terpene cyclization is orchestrated by terpene cyclases, which are involved in the biosynthesis of various cyclic natural products, but understanding origin and mechanism selectivity challenging. In this work, we describe an in-depth mechanistic study on cyclooctatin means theoretical calculations combined with experimental methods. We show that main framework formed through domino-type carbocation transportation along chain, call a “cation-stitching cascade”, including multiple...
Heterologous expression of four clade-A bifunctional terpene synthases (BFTSs), giving di/sesterterpenes with unique polycyclic carbon skeletons such as sesterfisherol, enabled the isolation sesterterpenes Bm1, Bm2, Bm3, and Pb1. Their structures suggested that formation products occurs via various diastereomeric carbocation intermediates, allowing proposal BFTSs catalyze three-step cyclizations using several stereofacial combinations allylic cation–olefin pairs in corresponding...
AndA, an Fe(II)/α-ketoglutarate (αKG)-dependent enzyme, is the key enzyme that constructs unique and congested bridged-ring system of anditomin (1), by catalyzing consecutive dehydrogenation isomerization reactions. Although we previously characterized AndA to some extent, means which facilitates this drastic structural reconstruction have remained elusive. In study, solved three X-ray crystal structures in its apo form complexes with Fe(II), αKG, two substrates. The mutational experiments...
Nearly pure populations of small hepatocytes (SHs), parenchymal (PHs), and nonparenchymal cells (NPCs) were prepared from the adult rat, cocultures NPCs reconstituted them first to obtain direct evidence that promote growth second compare potential between SHs PHs. PHs underwent multiple divisions when cocultured with NPCs, whereas neither nor formed colonies at 10 days cultured alone. Stellate in shown be responsible for this promotion. showed a higher capacity than To clearly show...
Amino acids play key roles in the function of central nervous system, and their alterations are implicated psychiatric disorders. In search for a biomarker major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino related molecules cerebrospinal fluid (CSF) 52 patients with MDD (42 depressed 10 remitted; DSM-IV) 54 matched controls. Significant differences were found four acid concentrations between After Bonferroni correction, only ethanolamine (EA)...
Abstract The cyclization mechanisms involved in the biosynthesis of sesterterpenes are not fully understood. For example, there two plausible reaction pathways for sesterfisherol biosynthesis, which differ order ring cyclization: A-D-B/C (Path a) and A-B-C/D b). It is difficult to capture intermediates terpene cyclization, a complex, domino-type reaction, so here we employed combination experimental computational methods. Density functional theory calculations revealed unexpected transition...
Non-canonical terpene synthases with primary sequences that are unrecognizable as canonical could be discovered through structural-model-based genome mining.
Nonenzymatic reactions sometimes construct complex structures observed in natural products, showing us unique chemical reactions. In our exploration of we identified a novel type isochromene-derived polyketide dimer 7 with 6/6/6/6/6 five-ring system from Chaetomium indicum along several new related polyketides. We demonstrated that isochromene 6 and its oxidized derivative 8 undergo nonenzymatic dimerization under acidic conditions to give 7. Furthermore, density functional theory (DFT)...
Triterpenes represent a crucial class of natural compounds with diverse biological activities and structural complexity. Among the various skeletal modifications in triterpene biosynthesis, formation seven-membered rings through ring expansion reactions significantly contributes to their diversity and, consequently, functional versatility. This study elucidates detailed reaction mechanism key via cyclopropane rearrangement biosynthesis ilelic acid. Using density theory (DFT) calculations, we...
The choline oxidase (CHOA) and betaine aldehyde dehydrogenase (BADH) genes identified in Aspergillus fumigatus are present as a cluster specific for fungal genomes. Biochemical molecular analyses of this showed that it has very biochemical functional features make unique different from its plant bacterial homologs. A. ChoAp catalyzed the oxidation to glycine with an intermediate reduced oxygen hydrogen peroxide using FAD cofactor. Badhp oxidized reduction NAD(+) NADH. Analysis AfchoAΔ::HPH...
One-bond <sup>199</sup>Hg–<sup>15</sup>N <italic>J</italic>-coupling.
Brasilane-type sesquiterpenes have been known for a long time, but their biosynthetic pathways and mechanisms remain elusive. Recently, two groups independently characterized Trichoderma terpene cyclase that produces trichobrasilenol, brasilane-type sesquiterpene, plausible pathway was proposed based on isotopic labeling experiments. In the mechanism, characteristic 5/6 bicyclic skeleton is synthesized from 5/7/3 tricyclic intermediate via complicated concerted reaction, including six...
Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the moiety. Although genetic analysis has indicated prenyltransferase LtmE and cytochrome P450 LtmJ involved in construction this structure, detailed mechanism remains to be elucidated. Herein, we report reconstitution biosynthetic pathway for lolitrems employing recently established genome-editing technique expression host Aspergillus oryzae. Heterologous bioconversion various intermediates revealed...