Research Topics
Genomes and GenesSpecies
| Tomohisa KuzuyamaSummaryAffiliation: University of Tokyo Country: Japan Publications
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Detail Information
Publications
An unusual isopentenyl diphosphate isomerase found in the mevalonate pathway gene cluster from Streptomyces sp. strain CL190K Kaneda
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo ku, Tokyo 113 0032, Japan
Proc Natl Acad Sci U S A 98:932-7. 2001..aureus and of the different enzymatic properties of mammalian (type 1) and S. aureus (type 2) isomerases, this unusual enzyme is considered to be a suitable molecular target for the screening of antibacterial drugs specific to S. aureus...
Diversity of the biosynthesis of the isoprene unitsTomohisa Kuzuyama
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo ku, Tokyo 113 0032, Japan
Nat Prod Rep 20:171-83. 2003..e type 2 IPP isomerase. The biosynthesis of terpenoids produced by actinomycetes is also reviewed. 117 references are cited...
Mevalonate and nonmevalonate pathways for the biosynthesis of isoprene unitsTomohisa Kuzuyama
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan
Biosci Biotechnol Biochem 66:1619-27. 2002..chem.qmw.ac.uk/iubmb/enzyme/reaction/terp/nonMVA.html...
Detection of the mevalonate pathway in Streptomyces species using the 3-hydroxy-3-methylglutaryl coenzyme A reductase geneTomohisa Kuzuyama
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan
J Antibiot (Tokyo) 55:919-23. 2002
Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilusAkira Horie
Biotechnology Research Center, The University of Tokyo, Bunkyo ku, Tokyo, Japan
Nat Chem Biol 5:673-9. 2009..This study thus reveals the previously unknown function of a small protein in primary metabolism...
Crystal structures of the regulatory subunit of Thr-sensitive aspartate kinase from Thermus thermophilusAyako Yoshida
Biotechnology Research Center, The University of Tokyo, Japan
FEBS J 276:3124-36. 2009..Comparison of the crystal structures of TtAKbeta and the regulatory subunit of C. glutamicum AK showed that the well-packed hydrophobic core and high Pro content in loops contribute to the high thermostability of TtAKbeta...
Mechanism of substrate recognition and insight into feedback inhibition of homocitrate synthase from Thermus thermophilusTakuya Okada
Biotechnology Research Center, University of Tokyo, Tokyo 113 8657, Japan
J Biol Chem 285:4195-205. 2010..Replacement of His-72 by leucine made HCS resistant to lysine inhibition, demonstrating the regulatory role of this conserved residue...
Unprecedented acetoacetyl-coenzyme A synthesizing enzyme of the thiolase superfamily involved in the mevalonate pathwayEiji Okamura
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
Proc Natl Acad Sci U S A 107:11265-70. 2010..This result suggests that nphT7 can be used to significantly increase the concentration of acetoacetyl-CoA in cells, eventually leading to the production of useful terpenoids and poly-beta-hydroxybutyrate...
Enhancement of the latent 3-isopropylmalate dehydrogenase activity of promiscuous homoisocitrate dehydrogenase by directed evolutionYumewo Suzuki
Biotechnology Research Center, University of Tokyo, Bunkyo ku, Japan
Biochem J 431:401-10. 2010..On the basis of the crystal structure, possible reasons for enhancement of the turnover number are discussed...
Structural Insight into concerted inhibition of alpha 2 beta 2-type aspartate kinase from Corynebacterium glutamicumAyako Yoshida
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
J Mol Biol 368:521-36. 2007..glutamicum. A putative Lys-binding site and the inhibitory mechanism of CgAK are discussed...
Mechanism for multiple-substrates recognition of alpha-aminoadipate aminotransferase from Thermus thermophilusTakeo Tomita
Biotechnology Research Center, The University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
Proteins 75:348-59. 2009..The crystal structures and site-directed mutagenesis revealed that intersubunit-electrostatic interactions contribute to the elevated thermostability of this enzyme...
NovQ is a prenyltransferase capable of catalyzing the addition of a dimethylallyl group to both phenylpropanoids and flavonoidsTaro Ozaki
Biotechnology Research Center, The University of Tokyo, Bunkyo ku, Tokyo, Japan
J Antibiot (Tokyo) 62:385-92. 2009..This study shows that NovQ can serve as a useful biocatalyst for the synthesis of prenylated phenylpropanoids and prenylated flavonoids...
Mechanism of concerted inhibition of alpha2beta2-type hetero-oligomeric aspartate kinase from Corynebacterium glutamicumAyako Yoshida
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
J Biol Chem 285:27477-86. 2010..This study shows not only the first crystal structures of alpha(2)beta(2)-type AK but also the mechanism of concerted inhibition in CgAK...
Functional characterization of the promiscuous prenyltransferase responsible for furaquinocin biosynthesis: identification of a physiological polyketide substrate and its prenylated reaction productsTakuto Kumano
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
J Biol Chem 285:39663-71. 2010..The promiscuous substrate specificity of Fur7 was demonstrated with respect to prenyl acceptor substrates and prenyl donor substrates. The steady-state kinetic constants of Fur7 with each prenyl acceptor substrate were also calculated...
Alteration of coenzyme specificity of lactate dehydrogenase from Thermus thermophilus by introducing the loop region of NADP(H)-dependent malate dehydrogenaseTakeo Tomita
Biotechnology Research Center, The University of Tokyo, Tokyo, Japan
Biosci Biotechnol Biochem 70:2230-5. 2006..The effect of the replacements on coenzyme specificity is discussed based on in silico simulation of the three-dimensional structure of the lactate dehydrogenase mutant...
The herbicide ketoclomazone inhibits 1-deoxy-D-xylulose 5-phosphate synthase in the 2-C-methyl-D-erythritol 4-phosphate pathway and shows antibacterial activity against Haemophilus influenzaeYukiko Matsue
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo, Japan
J Antibiot (Tokyo) 63:583-8. 2010..These data reveal the inhibitory mechanism of ketoclomazone on DXP synthase...
Chemoenzymatic syntheses of prenylated aromatic small molecules using Streptomyces prenyltransferases with relaxed substrate specificitiesTakuto Kumano
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
Bioorg Med Chem 16:8117-26. 2008..Kinetic studies with NphB reveal that the prenylation reaction follows a sequential ordered mechanism...
Structural basis for the alteration of coenzyme specificity in a malate dehydrogenase mutantTakeo Tomita
Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-8657, Japan
Biochem Biophys Res Commun 347:502-8. 2006....
Structural basis for leucine-induced allosteric activation of glutamate dehydrogenaseTakeo Tomita
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
J Biol Chem 286:37406-13. 2011..thermophilus GDH insensitive to leucine. Equivalent amino acid replacement caused a similar loss of sensitivity to leucine in human GDH2, suggesting that human GDH2 also uses the same allosteric site for regulation by leucine...
Dual roles of a conserved pair, Arg23 and Ser20, in recognition of multiple substrates in alpha-aminoadipate aminotransferase from Thermus thermophilusTakuya Ouchi
Biotechnology Research Center, The University of Tokyo, Yayoi, Bunkyo ku, Japan
Biochem Biophys Res Commun 388:21-7. 2009....
Hetero-oligomeric glutamate dehydrogenase from Thermus thermophilusTakeo Tomita
Biotechnology Research Center, Department of Biotechnology, The University of Tokyo, Tokyo 113 8657, Japan
Microbiology 156:3801-13. 2010..This study provides the first finding, to our knowledge, of a hetero-oligomeric GDH that can be regulated allosterically...
Involvement of the arginine repressor in lysine biosynthesis of Thermus thermophilusKei Fujiwara
Biotechnology Research Center, University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
Microbiology 152:3585-94. 2006..Furthermore, an alpha-galactosidase reporter assay for this promoter indicated that arginine repressed the promoter in an argR-dependent manner. These results indicate that lysine biosynthesis is regulated by arginine in T. thermophilus...
Bacillus subtilis ypgA gene is fni, a nonessential gene encoding type 2 isopentenyl diphosphate isomeraseMotoki Takagi
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan
Biosci Biotechnol Biochem 68:132-7. 2004..Disruption of the ypgA3 gene was not lethal to B. subtilis. These results indicate that Bacillus ypgA3 gene is fni, a nonessential gene encoding type 2 IPP isomerase...
Cloning and heterologous expression of the cyclooctatin biosynthetic gene cluster afford a diterpene cyclase and two p450 hydroxylasesSeung Young Kim
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
Chem Biol 16:736-43. 2009....
Crystal structure of tetrameric homoisocitrate dehydrogenase from an extreme thermophile, Thermus thermophilus: involvement of hydrophobic dimer-dimer interaction in extremely high thermotoleranceJunichi Miyazaki
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
J Bacteriol 187:6779-88. 2005..Both the crystal structure and the mutation analysis indicate that tetramer formation is involved in the extremely high thermotolerance of TtHICDH...
New glycosylated derivatives of versipelostatin, the GRP78/Bip molecular chaperone down-regulator, from Streptomyces versipellis 4083-SVS6Ping Zhao
Laboratory of Cell Biotechnology, Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo113 8657, Japan
Org Biomol Chem 7:1454-60. 2009..5 and 4.3 microM. These results suggest that the alpha-L-oleandropyranosyl (1-->4)-beta-D-digitoxopyranosyl residue in the sugar moiety may play an important role in down-regulating GRP78 expression induced by 2-deoxyglucose...
Two distinct pathways for essential metabolic precursors for isoprenoid biosynthesisTomohisa Kuzuyama
Biotechnology Research Center, The University of Tokyo, Tokyo, Japan
Proc Jpn Acad Ser B Phys Biol Sci 88:41-52. 2012..This review article focuses on our significant contributions to a comprehensive understanding of the biosynthesis of IPP and DMAPP...
Identification of 8-amino-2,5,7-trihydroxynaphthalene-1,4-dione, a novel intermediate in the biosynthesis of Streptomyces meroterpenoidsShota Isogai
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Tokyo 113 8657, Japan
Bioorg Med Chem Lett 22:5823-6. 2012..We propose that the biosynthetic pathway generating 8-amino-flaviolin is the common route for the biosynthesis of Streptomyces meroterpenoids...
Purification, crystallization and preliminary X-ray analysis of the regulatory subunit of aspartate kinase from Thermus thermophilusAyako Yoshida
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
Acta Crystallogr Sect F Struct Biol Cryst Commun 63:96-8. 2007..Diffraction data were collected to 2.15 A at a synchrotron source. The crystal belongs to the cubic space group P4(3)32 or P4(1)32, with unit-cell parameters a = b = c = 141.8 A...
Nucleotide sequences of genes encoding allosamidin-sensitive and -insensitive chitinases produced by allosamidin-producing StreptomycesHiroshi Matsuura
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan
Biosci Biotechnol Biochem 67:2002-5. 2003..AJ9463. In this study, we cloned and sequenced the genes encoding the two chitinases, which clarified that chitinase S and IS belong to the family 18 and 19 chitinase, respectively...
Elicitor induced activation of the methylerythritol phosphate pathway toward phytoalexins biosynthesis in riceAtsushi Okada
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Tokyo, Japan
Plant Mol Biol 65:177-87. 2007..These results suggest that activation of the MEP pathway is required to supply sufficient terpenoid precursors for the production of phytoalexins in infected rice plants...
[Overlooked targets for the development of antibacterial and antimalarial drugs and herbicides: diverse biosynthetic systems for the isoprene units]Motoki Takagi
Tanpakushitsu Kakusan Koso 47:58-65. 2002
[Biosynthesis of a hybrid terpenoid polyketide-derived natural product and production of useful prenylated compounds by using prenyltransferase]Tomohisa Kuzuyama
Tanpakushitsu Kakusan Koso 52:1736-41. 2007
Heterologous mevalonate production in Streptomyces lividans TK23Tomohisa Kuzuyama
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Japan
Biosci Biotechnol Biochem 68:931-4. 2004..strain CL190...
Novel Tryptophan Metabolism by a Potential Gene Cluster That Is Widely Distributed among ActinomycetesTaro Ozaki
From the Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
J Biol Chem 288:9946-56. 2013..Finally, dehydration of 5-DMAIAOx presumably occurs to yield 5-DMAIAN. This study provides insight into the biosynthesis of prenylated indoles that have been purified from actinomycetes...
Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeletonAyuko Meguro
Biotechnology Research Center, The University of Tokyo, 1 1 1 Yayoi, Tokyo 113 8657, Japan
Chembiochem 14:316-21. 2013..SANK 60404. DtcycA and DtcycB are novel bacterial diterpene cyclases for the synthesis of the cembrane skeleton...
Leader peptide-mediated transcriptional attenuation of lysine biosynthetic gene cluster in Thermus thermophilusTaishi Tsubouchi
Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
J Biol Chem 280:18511-6. 2005..This is the first report demonstrating the transcriptional regulation of amino acid biosynthesis in T. thermophilus...
Crystal structure of NAD-dependent malate dehydrogenase complexed with NADP(H)Takeo Tomita
Biotechnology Research Center, The University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
Biochem Biophys Res Commun 334:613-8. 2005..This has provided the first evidence for the alternative binding mode of the nicotinamide coenzyme, that has pseudo-symmetry in its structure, in a single enzyme...
fldA is an essential gene required in the 2-C-methyl-D-erythritol 4-phosphate pathway for isoprenoid biosynthesisKia Joo Puan
Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Group in Immunology, University of Iowa, EMRB 340F, Iowa City, IA 52242, USA
FEBS Lett 579:3802-6. 2005..Thus, the essential role for flavodoxin I in E. coli is in the MEP pathway for isoprenoid biosynthesis...
Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis in ArabidopsisKazunori Okada
Department of Biology, Tokyo Gakugei University, Nukuikitamachi 4 1 1, Koganei Shi, Tokyo, 184 8501, Japan
Planta 215:339-44. 2002..These observations suggest that both AtMECT and DXR are important in the synthesis of isopentenyl diphosphate and dimethylallyl diphosphate and that ent-kaurene is mainly produced through the nonmevalonate pathway in the plastid...
Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase complexed with cofactors: implications of a flexible loop movement upon substrate bindingShunsuke Yajima
Department of Bioscience, Tokyo University of Agriculture, Setagaya Ku, Tokyo 156 8502, Japan
J Biochem 131:313-7. 2002..A flexible loop covering the substrate binding site plays an important role in the enzymatic reaction and the determination of substrate specificity...
Cloning and functional characterization of 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (GbMECT) gene from Ginkgo bilobaSang-Min Kim
Program in Applied Life Chemistry, School of Agricultural Biotechnology, Seoul National University, Sinlim-dong, Gwanak-gu, Seoul 151-921, Republic of Korea; Plant Metabolism Research Center, Kyung Hee University, Yongin 449-701, Republic of Korea
Phytochemistry 67:1435-41. 2006..Full 88 N-terminal residues were necessary to deliver the protein into the chloroplast as shown by protein-targeting analysis with GFP as a reporter protein in Arabidopsis thaliana protoplasts...
A relationship between the mevalonate pathway and isoprenoid production in actinomycetesTakashi Kawasaki
Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan
J Antibiot (Tokyo) 56:957-66. 2003..This result suggested that the presence of the mevalonate pathway might be a good landmark to detect the production of isoprenoid compounds by actinomycetes...
Structural basis for the promiscuous biosynthetic prenylation of aromatic natural productsTomohisa Kuzuyama
Jack Skirball Chemical Biology and Proteomics Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
Nature 435:983-7. 2005..These crystal structures, coupled with in vitro assays, provide a basis for understanding and potentially manipulating the regio-specific prenylation of aromatic small molecules using this structurally unique family of aromatic PTases...
Presence of copalyl diphosphate synthase gene in an actinomycete possessing the mevalonate pathwayTakashi Kawasaki
Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan
J Antibiot (Tokyo) 57:739-47. 2004..These results again showed that actinomycetes possessing the mevalonate pathway usually produce an isoprenoid and that its biosynthetic gene cluster exists in adjacent the mevalonate pathway gene cluster...
Biosynthesis of a natural polyketide-isoprenoid hybrid compound, furaquinocin A: identification and heterologous expression of the gene clusterTakashi Kawasaki
Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan
J Bacteriol 188:1236-44. 2006....
Functional analysis of eubacterial diterpene cyclases responsible for biosynthesis of a diterpene antibiotic, terpentecinYoshimitsu Hamano
Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398, Japan
J Biol Chem 277:37098-104. 2002..These results suggested that an actual reaction catalyzed by the ORF12 was the conversion of TDP into TTE in vivo...
Preferential recognition of a microbial metabolite by human Vgamma2Vdelta2 T cellsKia Joo Puan
Division of Rheumatology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa College of Medicine, EMRB 400F, Iowa City, IA 52242, USA
Int Immunol 19:657-73. 2007..This preferential stimulation by a common microbial isoprenoid metabolite allows Vgamma2Vdelta2 T cells to respond to a broad array of pathogens using this pathway...
Interconversion of the product specificity of type I eubacterial farnesyl diphosphate synthase and geranylgeranyl diphosphate synthase through one amino acid substitutionTakashi Kawasaki
Biotechnology Research Center, Toyama Prefectural University, Toyama 939-0398
J Biochem (Tokyo) 133:83-91. 2003..These results showed that the amino acid residue at the 57th (58th) position after the FARM also played an important role in determination of the product specificity...
Crystal structure of 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase, an enzyme in the non-mevalonate pathway of isoprenoid synthesisTakashi Wada
Genomic Sciences Center, RIKEN Yokohama Institute, and Protein Design Laboratory, Yokohama City University, 1 7 29 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
J Biol Chem 278:30022-7. 2003..Assaying the enzyme showed that CDP-ME kinase will phosphorylate CDP-ME but not 4-(uridine 5'-diphospho)-2-C-methyl-D-erythritol, indicating the substrate pyrimidine moiety is involved in important interactions with the enzyme...
Structure and catalytic mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECDP) synthase, an enzyme in the non-mevalonate pathway of isoprenoid synthesisHiroyuki Kishida
Protein Design Laboratory, Graduate School of Integrated Science, Yokohama City University, 1 7 29 Suehiro cho, Tsurumi, Yokohama 230 0045, Japan
Acta Crystallogr D Biol Crystallogr 59:23-31. 2003..At the high resolution of the refinement (1.6 A) the positions and coordination of the magnesium ions in the active site are clearly seen...
Mechanistic studies of HPP epoxidase: configuration of the substrate governs its enzymatic fateZongbao Zhao
Division of Medicinal Chemistry, College of Pharmacy, Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712, USA
Angew Chem Int Ed Engl 41:4529-32. 2002
Contribution of the mevalonate and methylerythritol phosphate pathways to the biosynthesis of gibberellins in ArabidopsisHiroyuki Kasahara
Laboratory for Cellular Growth and Development, Growth Physiology Research Group, Plant Science Center, RIKEN (The Institute of Physical and Chemical Research, Hirosawa 2-1, Wako, Saitama 351-0198, Japan
J Biol Chem 277:45188-94. 2002..We also provide evidence to suggest that the MVA pathway still contributes to GA biosynthesis when this pathway is limiting...
Cloning and characterization of 2-C-methyl-D: -erythritol 2,4-cyclodiphosphate synthase (MECS) gene from Ginkgo bilobaSang-Min Kim
Program in Applied Life Chemistry, School of Agricultural Biotechnology, Seoul National University, Seoul, 151-921, Korea
Plant Cell Rep 25:829-35. 2006....
Growth-phase dependent expression of the mevalonate pathway in a terpenoid antibiotic-producing Streptomyces strainYoshimitsu Hamano
Biotechnology Research Center, Toyama Prefectural University, Japan
Biosci Biotechnol Biochem 66:808-19. 2002....
Identification of class 2 1-deoxy-D-xylulose 5-phosphate synthase and 1-deoxy-D-xylulose 5-phosphate reductoisomerase genes from Ginkgo biloba and their transcription in embryo culture with respect to ginkgolide biosynthesisSang-Min Kim
School of Agricultural Biotechnology, Seoul National University, Korea
Planta Med 72:234-40. 2006..Exclusive transcription of ginkgolide biosynthesis-specific LPS and GbDXS2 in roots and the appearance of ginkgolides in leaves was consistent with translocation of the compounds from roots to leaves...
Structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycinShunsuke Yajima
Department of Bioscience, Tokyo University of Agriculture, Setagaya Ku, Tokyo, Japan
Acta Crystallogr Sect F Struct Biol Cryst Commun 63:466-70. 2007..On the other hand, no electron density was observed for the nicotinamide-ribose portion of NADPH and the position of Asp149 anchoring Mg(2+) was shifted by NADPH in the active site...
