A5004541812- Microbial Natural Products and Biosynthesis
- Carbohydrate Chemistry and Synthesis
- Enzyme Structure and Function
- Biochemical and Molecular Research
- Plant biochemistry and biosynthesis
- Synthetic Organic Chemistry Methods
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Production and Characterization
- Microbial Metabolism and Applications
- Fungal Biology and Applications
- Marine Sponges and Natural Products
- Vitamin D Research Studies
- Metalloenzymes and iron-sulfur proteins
- Photosynthetic Processes and Mechanisms
- Fluorine in Organic Chemistry
- Enzyme Catalysis and Immobilization
- Analytical Chemistry and Chromatography
- Metal-Catalyzed Oxygenation Mechanisms
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
Tokyo Institute of Technology
2016-2025
Institute of Science Tokyo
2025
Kameda Medical Center
2021-2024
Shinshu University
2021-2022
Saga University
2015
Denso (United States)
2015
Japan Synchrotron Radiation Research Institute
2011
University of Oklahoma
2008
Juntendo University
2007-2008
Keio University
2007
Rapamycin (Rap) and its derivatives, called rapalogs, are being explored in clinical trials targeting cancer neurodegeneration. The underlying mechanisms of Rap actions, however, not well understood. Mechanistic target rapamycin (mTOR), a lysosome-localized protein kinase that acts as critical regulator cellular growth, is believed to mediate most actions. Here, we identified mucolipin 1 (transient receptor potential channel [TRPML1], also known MCOLN1), the principle Ca2+ release lysosome,...
Summary Although modern MS has facilitated the advent of metabolomics, some natural products such as carotenoids are not readily compatible to detection by MS. In present article, we describe how matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI/TOF‐MS) can be utilized acquire spectra effectively. The procedure is sensitive (pmole range), reduces ‘spot spot’ variation and provides high accuracy, thus aiding identification. technique been applied in vivo...
Acyltransferases (ATs) are key determinants of building block specificity in polyketide biosynthesis. Despite the importance protein-protein interactions between AT and acyl carrier protein (ACP) during acyltransfer reaction, mechanism ACP recognition by is not understood detail. Herein, we report crystal structure VinK, which transfers a dipeptide group two ACPs, VinL VinP1LdACP, vicenistatin The isolated VinK showed unique substrate-binding pocket for linked to ACP. To gain greater insight...
BtrN encoded in the butirosin biosynthetic gene cluster possesses a CXXXCXXC motif conserved within radical S-adenosyl methionine (SAM) superfamily. Its disruption producer Bacillus circulans caused interruption of pathway between 2-deoxy-scyllo-inosamine (DOIA) and 2-deoxystreptamine (DOS). Further, vitro assay overexpressed enzyme revealed that catalyzed oxidation DOIA under strictly anaerobic conditions along with consumption an equimolar amount SAM to produce 5'-deoxyadenosine,...
Macrolactam antibiotics are an important class of macrocyclic polyketides that contain a unique nitrogen-containing starter unit. In the present study, set biosynthetic enzymes in macrolactam antibiotic vicenistatin was characterized. We found protection-deprotection strategy aminoacyl-ACP intermediate critical this system. On basis bioinformatics, described pathway is also proposed as common method for carrying amino acids biosynthesis other antibiotics.
The last step of neomycin biosynthesis is the epimerization at C-5‴ C to give B. A candidate enzyme responsible for was a putative radical S-adenosyl-l-methionine (SAM) enzyme, NeoN, which uniquely encoded in biosynthetic gene cluster and remained an unassigned protein biosynthesis. reconstituted reduced NeoN showed expected activity presence SAM. In epimerization, 1 equiv SAM consumed convert into site reactive toward clearly confirmed be by detecting incorporation deuterium atom from...
Modular polyketide synthases (PKSs) are multi‐domain enzymes involved in the biosynthesis of natural products. The dehydratase (DH) domain catalyzes dehydration β‐hydroxyacyl unit attached to acyl carrier protein (ACP) modular PKS. Although DH likely recognizes cognate ACP during reaction, molecular basis DH–ACP interactions remains elusive. In this study, we conducted cross‐linking analysis using a pantetheine‐type probe for investigating recognition fusion‐DH generated from split‐DH...
The petroleum ether extract of the seeds Annona squamosa L. yielded thirteen adjacent and four non-adjacent bis-tetrahydrofuranic acetogenins, in addition to squamocin (1) squamostatin-A. structures named as squamocins-B (2), -C (3), -D (4), -E (5), -F (6), -G (7), -H (8), -I (9), -J (10), -K (11), -L(12), -M (13) -N (14), have been established on basis spectral evidence. Squamocins-B, -D, -E, -F, -I, are new acetogenins. these acetogenins vary hte carbon number (C37 or C35), position...
Squamocin, a new trihydroxy-bis-tetrahydrofuran fatty acid γ-lactone (acetogenin), has been isolated from Annona squamosa L.(Annonaceae) and its structure elucidated on the basis of spectral evidence chemical degradations.
Now found in bacteria: An increasing number of genome sequences indicate that bacteria possess a variety terpenoid cyclase genes. The characterization two sesquiterpene (SC) genes the draft sequence Streptomyces citricolor is described here. Our study strongly supports idea mining useful approach revealing diversity bacteria.
Abstract Cremimycin is a 19‐membered macrolactam glycoside antibiotic based on three distinctive substructures: 1) β‐amino fatty acid starter moiety, 2) bicyclic ring, and 3) cymarose unit. To elucidate the biosynthetic machineries responsible for these structures, cremimycin gene cluster was identified. The cmi consists of 33 open reading frames encoding eight polyketide synthases, six deoxysugar enzymes, characteristic group five β‐amino‐acid‐transfer enzymes. Involvement in production...
Adenylation enzymes play important roles in the biosynthesis and degradation of primary secondary metabolites. Mechanistic insights into recognition α-amino acid substrates have been obtained for adenylation enzymes. The Asp residue is invariant essential stabilization group substrate. In contrast, β-amino mechanism still unclear despite importance activation various natural products. Herein, we report crystal structure stand-alone enzyme VinN, which specifically activates...
Abstract Hitachimycin is a macrolactam antibiotic with ( S )‐β‐phenylalanine (β‐Phe) at the starter position of its polyketide skeleton. To understand incorporation mechanism β‐Phe and modification unique skeleton, biosynthetic gene cluster for hitachimycin in Streptomyces scabrisporus was identified by genome mining. The contains putative phenylalanine‐2,3‐aminomutase (PAM), five synthases, four β‐amino‐acid‐carrying enzymes, characteristic amidohydrolase. A hitA knockout mutant showed no...
Acyltransferases (ATs) are responsible for the selection and incorporation of acyl building blocks in biosynthesis various polyketide natural products. The trans-AT modular synthases have a discrete trans-acting AT loading an unit onto carrier protein (ACP) located within each module. Despite importance protein–protein interactions between ATs ACPs assembly lines, dynamic actions remain largely uncharacterized because inherently transient nature ACP–enzyme interactions. Herein, we report...
A methylcobalamin (MeCbl)-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase Fom3 was found to catalyze the C-methylation of cytidylyl-2-hydroxyethylphosphonate (HEP-CMP) give cytidylyl-2-hydroxypropylphosphonate (HPP-CMP), although it originally proposed 2-hydroxyethylphosphonate 2-hydroxypropylphosphonate in biosynthesis a unique C–P bond containing antibiotic fosfomycin Streptomyces. Unexpectedly, reaction product from HEP-CMP almost 1:1 diastereomeric mixture HPP-CMP,...