研究领域

Natural Product Chemistry/Bioorganic Chemistry/Biochemistry

Natural product biosynthesis has long been affording interesting and important organic compounds. The biosynthetic systems are apparently sorts of designer nano-assembly line. Recent advances in genetics and molecular biology as well as chemical technology, will be beneficial in understanding the precise nature of the biosynthetic machinery and in engineering the machinery to produce natural and unnatural products. My group is currently working in the following general research areas with focus on elucidationg the mechanism of formation of a wide variety of bioactive natural products from microbial origins. Research Topics： Search for Bioactive Natural Products (isolation, structure elucidation, synthesis) Biosynthesis of Natural Products (genome mining, engineered biosynthesis) Enzyme Mechanistic Study (structure-based engineering, mechanistic studies)

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Kudo, F.; Kawamura, K.; Uchino, A.; Miyanaga, A.; Numakura,M.; Takayanagi, R.; Eguchi, T. Genome Mining of Hitachimycin Biosynthetic Gene Cluster; Involvement of Phenylalanine-2,3-aminomutase in the Biosynthesis. ChemBioChem, in press. Yamada, Y.; Arima, S.; Nagamitsu, T.; Johmoto, K.; Uekusa, H.; Eguchi, T.; Shin-ya, K.; Cane,D. E.; Ikeda, H. Novel Terpenes Generated by Heterologous Expression of Bacterial Terpene Synthase Genes in an Engineered Streptomyces Host. J. Antibiot., in press. Takeishi, R.; Kudo, F.; Numakura, M.; Eguchi, T. Epimerization at C-3’’ in Butirosin Biosynthesis by an NAD(+)-Dependent Dehydrogenase BtrE and an NADPH-Dependent Reductase BtrF. ChemBioChem, 2015, 16, 487-495. Miyanaga, A.; Cieślak, J.; Shinohara, Y.; Kudo, F.; Eguchi, T. The Crystal Structure of Adenylation Enzyme VinN Reveals a Unique β-Amino Acid Recognition Mechanism. J. Biol. Chem., 2014, 289, 31448-31457. Kudo, F.; Hoshi, S.; Kawashima, T.; Kamachi, T.; Eguchi, T. Characterization of a Radical S-Adenosyl-L-methionine Epimerase, NeoN, in the Last Step of Neomycin B Biosynthesis. J. Am. Chem. Soc., 2014, 136, 13909-13915. 工藤史貴、宮永顕正、江口正、 β-アミノ酸含有マクロラクタム抗生物質の生合成． 化学と生物、2014, 52, 830-835． 江口正、微生物二次代謝産物生合成の精密解析. The Japanese Journal of Antibiotics, 2014, 67, 253-263. Kudo, F.; Miyanaga, A.; Eguchi, T. Biosynthesis of Natural Products containing β-Amino Acids. Nat. Prod. Rep., 2014, 31, 1056-1073. Shinohara, Y.; Miyanaga, A.; Kudo, F.; Eguchi, T. The Crystal Structure of the Amidohydrolase VinJ Shows a Unique Hydrophobic Tunnel for its Interaction with Polyketide Substrates. FEBS Lett., 2014, 588, 995-1000. Koide, M.; Miyanaga, A.; Kudo, F.; Eguchi, T. Characterization of Polyphosphate Glucokinase SCO5059 from Streptomyces coelicolor A3(2). Biosci. Biotechnol. Biochem., 2013, 77, 2322-2324. Amagai, K.; Takaku, R.; Kudo, F.; Eguchi, T. A Unique Amino Transfer Mechanism for Constructing the β-Amino Fatty Acid Starter Unit in the Biosynthesis of Macrolactam Antibiotic Cremimycin. ChemBioChem, 2013, 14, 1998-2006. Takaishi,M.; Kudo, F.; Eguch, T. Identification of Incednine Biosynthetic Gene Cluster: Characterization of Novel β-Glutamate-β-decarboxylase IdnL3. J. Antibiot., 2013, 66, 691-699. Hirayama, A.; Eguchi, T.; Kudo,F. A Single PLP-Dependent Enzyme PctV Catalyzes the Transformation of 3-Dehydroshikimate into 3-Aminobenzoate in the Biosynthesis of Pactamycin. ChemBioChem, 2013, 14, 1198-1203. Itagaki, S.; Haga, M.; Oikawa, Y.; Sakoda, A.; Ohke, Y.; Sawada, H.; Eguchi, T.; Tamega, H.Difference on the Roles of of Glutamine Amidotransferase Subunit of Pyridoxal 5'-Phosphate Synthase between Bacillus circulans and Bacillus subtilis. Biosci. Biotechnol. Biochem., 2013, 77, 1482-1485. Takaishi, M.; Kudo, F.; Eguchi, T. A Unique Pathway for the 3-Aminobutyrate Starter Unit from L-Glutamate through β-Glutamate during Biosynthesis of the 24-Membered Macrolactam Antibiotic, Incednine. Org. Lett., 2012, 14, 4591-4593. Fukuda, H.; Nishiyama, Y.; Nakamura, N.; Ohno, Y.; Eguchi, T.; Iwabuchi, Y.; Usui, T.; Kanoh, N. Synthesis and Structure-Activity Relationship of Vicenistatin, a Cytotoxic 20-Membered Macrolactam Glycoside. Chem. Asian J., 2012, 7, 2872-2881. Kudo, F.; Yusaku Asou, Y.; Watanabe, M.; Kitayama,T.; Eguchi, T. Potent Oligomerization and Macrocyclization Activity of the Thioesterase Domain of Vicenistatin Polyketide Synthase. Synlett, 2012, 23, 1843-1846. Sucipto, H.; Kudo, F.; Eguchi, T. The Last Step of Kanamycin Biosynthesis: Unique Deamination Reaction Catalyzed by the alpha-Ketoglutarate-dependent Nonheme Iron Dioxygenase KanJ and the NADPH Dependent Reductase KanK. Angew. Chem. Int. Ed., 2012, 51, 3428-3431. Shinohara, Y.; Kudo, F.; Eguchi, T. A Natural Protecting Group Strategy To Carry an Amino Acid Starter Unit in the Biosynthesis of Macrolactam Polyketide Antibiotics. J. Am. Chem. Soc., 2011, 133, 18134–18137. Amagai, K.; Kudo, F.; Eguchi, T. Biosynthetic Pathway of Macrolactam Polyketide Antibiotic Cremimycin. Tetrahedron, 2011, 67, 8559-8563.　 Nakano, C.; Kudo, F.; Eguchi, T.; Ohnishi, Y. Genome Mining Reveals Two Novel Bacterial Sesquiterpene Cyclases: (-)-epi-α-Bisabolol and (-)-Germacradiene-4-ol Synthases from Streptomyces citricolor. ChemBioChem, 2011, 12, 2271-2275. Nango, E.; Yamamoto, T.; Kumasaka, T.; Eguchi, T. Structure of Thermus thermophilus Homoisocitrate Dehydrogenase in Complex with a Designed Inhibitor. J. Biochem., 2011, 150, 607-614 .