A5021597347- Microbial Natural Products and Biosynthesis
- Plant biochemistry and biosynthesis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Fungal Biology and Applications
- Spaceflight effects on biology
- Natural product bioactivities and synthesis
- Synthetic Organic Chemistry Methods
- Carbohydrate Chemistry and Synthesis
- Microbial Metabolic Engineering and Bioproduction
- Marine Sponges and Natural Products
- Microbial Metabolism and Applications
- Bone Metabolism and Diseases
- Lung Cancer Treatments and Mutations
- Cancer Diagnosis and Treatment
- Lung Cancer Diagnosis and Treatment
- Nausea and vomiting management
- Wind and Air Flow Studies
- Crystallography and molecular interactions
- Phytochemical compounds biological activities
- Bone health and treatments
- Chemical Synthesis and Analysis
- Alkaloids: synthesis and pharmacology
- Bioactive Compounds and Antitumor Agents
- Chemical synthesis and alkaloids
RIKEN Center for Sustainable Resource Science
2016-2025
Saitama University
2021-2024
RIKEN
2011-2024
The University of Tokyo
1990-2020
Kobe University Hospital
2014-2017
Yamagata University Hospital
1995-2017
Japanese Foundation For Cancer Research
1994-2016
Antibiotic Research UK
2013
Aichi Cancer Center
2013
RIKEN Advanced Science Institute
2009-2012
Several eubacteria including Esherichia coli use an alternative nonmevalonate pathway for the biosynthesis of isopentenyl diphosphate instead ubiquitous mevalonate pathway. In pathway, 2- C -methyl- d -erythritol or its 4-phosphate, which is proposed to be formed from 1-deoxy- -xylulose 5-phosphate via intramolecular rearrangement followed by reduction process, one biosynthetic precursors diphosphate. To clone gene(s) responsible synthesis we prepared and selected E. mutants with obligatory...
Abstract Polyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding gene cluster evolution provides a rationale for reprogramming the biosynthetic machinery. Herein, we report characterization giant modular polyketide synthases (PKSs) responsible production aminopolyol polyketides. Heterologous expression over 150 kbp clusters successfully afforded products, whose stereochemistry was established by taking...
The acetal (O-glycoside) bonds of glycans and glycoconjugates are chemically biologically vulnerable, therefore C-glycosides interest as more stable analogs. We hypothesized that, if the O-glycoside linkage plays a vital role in glycan function, biological activities C-glycoside analogs would vary depending on their substituents. Based this idea, we adopted "linkage-editing strategy" for creation (pseudo-glycans). designed three types pseudo-glycans with CH2 CHF linkages, which resemble...
Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from cell tumors as model to examine the that IL-6 may play human resorption. We found conditioned medium 24-h cultures highly purified cells (10(6)/ml) contained large amounts (37.9 +/- 8.8 ng/ml), similar amount produced by tumor stromal (29.8 11.5 ng/ml). Giant and expressed mRNA,...
Abstract Terpenes are structurally diverse compounds that of interest because their biological activities and industrial value. These consist chirally rich hydrocarbon backbones derived from terpene synthases, which subsequently decorated with hydroxyl substituents catalyzed by hydroxylases. Availability these is, however, limited intractable synthetic means they produced in low amounts as complex mixtures natural sources. We engineered yeast for sesquiterpene accumulation introducing...
Solavetivone, a potent antifungal phytoalexin, is derived from vetispirane-type sesquiterpene, premnaspirodiene, by putative regio- and stereo-specific hydroxylation, followed second oxidation to yield the α,β-unsaturated ketone. Mechanistically, these reactions could occur via single, multifunctional cytochrome P450 or some combination of P450s dehydrogenase. We report here characterization single enzyme, Hyoscyamus muticus premnaspirodiene oxygenase (HPO), that catalyzes successive at...
ABSTRACT In addition to the ubiquitous mevalonate pathway, Streptomyces sp. strain CL190 utilizes nonmevalonate pathway for isopentenyl diphosphate biosynthesis. The initial step of this is formation 1-deoxy- d -xylulose 5-phosphate (DXP) by condensation pyruvate and glyceraldehyde 3-phosphate catalyzed DXP synthase. corresponding gene, dxs , was cloned from using PCR with two oligonucleotide primers synthesized on basis highly conserved regions among homologs six genera. gene encodes 631...
Calcitonin inhibits both osteoclast formation and bone resorption, is a primary treatment for patients with hypercalcemia increased turnover. However, the clinical utility of calcitonin limited because become refractory to after several days (the "escape phenomenon"). The molecular basis "escape" unclear. To determine regulatory mechanisms controlling receptor (CTR) expression in osteoclasts their precursors, we treated immature mononuclear precursors human osteoclast-like multinucleated...
1-Deoxy-d-xylulose 5-phosphate (DXP) reductoisomerase, which simultaneously catalyzes the intramolecular rearrangement and reduction of DXP to form 2-C-methyl-d-erythritol 4-phosphate, constitutes a key enzyme an alternative mevalonate-independent pathway for isopentenyl diphosphate biosynthesis. The dxrgene encoding this from Escherichia coli was overexpressed as histidine-tagged protein characterized in detail. DNA sequencing analysis dxr genes 10E. dxr-deficient mutants revealed base...
Autocrine products of osteoclasts such as interleukin-6 may play an important role in normal osteoclast formation and activity.To identify novel stimulatory factors for osteoclasts, we have prepared a mammalian cDNA expression library generated from highly purified human osteoclast-like multinucleated cells (MNC) formed long term bone marrow cultures screened this autocrine that enhance MNC formation.A candidate clone which stimulated was isolated.Sequence analysis showed encoded annexin I1...
Fumitremorgin C, a diketopiperazine mycotoxin produced by Aspergillus fumigatus, is potent and specific inhibitor of breast cancer resistance protein (BCRP). Elucidation the fumitremorgin C biosynthetic pathway provides strategy for new drug design. A structure-activity relationship study based on metabolites related to ftm gene cluster revealed that process most crucial inhibitory activity against BCRP was cyclization form C. To determine involved in reaction, targeted inactivation...
Genome sequencing of Streptomyces species has highlighted numerous potential genes secondary metabolite biosynthesis. The mining cryptic is important for exploring chemical diversity. Here we report the metabolite-guided genome and functional characterization a gene by biochemical studies. Based on systematic purification metabolites from sp. SN-593, isolated novel compound, 6-dimethylallylindole (DMAI)-3-carbaldehyde. Although many 6-DMAI compounds have been variety organisms, an enzyme...
Enzyme-catalyzed [4+2] cycloaddition has been proposed to be a key transformation process in various natural product biosynthetic pathways. Recently Fsa2 was found involved stereospecific trans-decalin formation during the biosynthesis of equisetin, potent HIV-1 integrase inhibitor. To understand mechanisms by which fsa2 determines stereochemistry reaction products, we sought an homologue that is pathway enantiomerically opposite analogue, and phm7, phomasetin. A decalin skeleton with...
American phase I studies have reported that the recommended dose of TAS-102 (trifluridine/tipiracil) was 25 mg/m(2) twice a day (b.i.d.), although this schedule did not provide clinically relevant improvements in II study advanced gastric cancer (AGC). However, pivotal III revealed at 35 b.i.d. provided improvement overall survival (OS) among patients with metastatic colorectal cancer. Therefore, we re-evaluated efficacy, safety, and pharmacokinetic parameters b.i.d Japanese AGC.All had...
Abstract Esterified drimane-type sesquiterpene lactones such as astellolides display various biological activities and are widely produced by plants fungi. Given their low homology to known cyclases, the genes responsible for biosynthesis have not been uncovered yet. Here, we identified astellolide gene cluster from Aspergillus oryzae discovered a novel biosynthetic machinery consisting of AstC, AstI, AstK. All these enzymes annotated haloacid dehalogenase-like hydrolases, whereas AstC also...