工藤史貴研究室
（生体反応化学研究室）

2024年以降の主論文

2025年

  1. Kotagiri, K; Tachibana, H; Kawasaki, D; Chisuga, T; Kashima, T; Fushinobu, S; Kudo, F; *Eguchi, T; *Miyanaga, A, Elucidation of interface interactions between a dehydratase domain and an acyl carrier protein in cremimycin polyketide synthase, FEBS Lett., 599(8), 1159-1168, 2025, DOI: 10.1002/1873-3468.15103.

2024年

  1. *Kudo, F, Biosynthesis of macrolactam antibiotics with β-amino acid polyketide starter units, J Antibiot. 77(8), 486-498, 2024, DOI: 10.1038/s41429-024-00742-2.
  2. *Kudo, F; Tsuboi, K; Ikezaki, M; Nagayama, D; Kawamura, K; Ando, T; Miyanaga, A; *Eguchi, T, The Post-Polyketide Synthase Modification Mechanism in Hitachimycin Biosynthesis, ChemBioChem, 25, e202400405, 2024, DOI: 10.1002/cbic.202400405.
  3. Wang D; *Miyanaga, A; Chisuga, T; *Kudo, F; *Eguchi, T, Engineering the Substrate Specificity of (S)-β-Phenylalanine Adenylation Enzyme HitB, ChemBioChem, 25, e202400383, 2024, DOI: 10.1002/cbic.202400383.
  4. *Ishikawa, F; Nohara, M; Miyanaga, A; Kuramoto, S; Miyano, N; Asamizu, S; Kudo, F; Onaka, H; Eguchi, T; *Tanabe, G, Biosynthetic Incorporation of Non-native Aryl Acid Building Blocks into Peptide Products Using Engineered Adenylation Domains, ACS Chem Biol, 19(12), 2569-2579, 2024, DOI: 10.1021/acschembio.4c00663.

2023年以前の主論文（2003年〜）

ポリケチド系天然物の生合成研究

  1. *Kudo, F; Kishikawa, K; Tsuboi, K; Kido, T; Usui, T; Hashimoto, J; Shin-ya, K; Miyanaga, A; *Eguchi, T, Acyltransferase Domain Exchange between Two Independent Type I Polyketide Synthases in the Same Producer Strain of Macrolide Antibiotics, ChemBioChem, 24, e202200670, 2023, DOI: 10.1002/cbic.202200670
  2. *Kudo, F; Takahashi, S; Miyanaga, A; Nakazawa, Y; Nishino, K; Hayakawa, Y; Kawamura, K; Ishikawa, F; Tanabe, G; Iwai, N; Nagumo, Y; Usui, T; *Eguchi, T, Mutational Biosynthesis of Hitachimycin Analogs Controlled by the β-Amino Acid-Selective Adenylation Enzyme HitB, ACS Chem. Biol., 16(3), 539–547, 2021, DOI: 10.1021/acschembio.1c00003.
  3. Kawasaki, D; Miyanaga, A; Chisuga, T; Kudo, F; *Eguchi, T, Functional and Structural Analyses of the Split-Dehydratase Domain in the Biosynthesis of Macrolactam Polyketide Cremimycin, Biochemistry, 58(48), 4799–4803, 2019, DOI: 10.1021/acs.biochem.9b00897.
  4. Miyanaga, A; Kudo, F; *Eguchi, T, Mechanisms of β-amino acid incorporation in polyketide macrolactam biosynthesis, Curr. Opin. Chem. Biol., 35, 58–64, 2016, DOI: 10.1016/j.cbpa.2016.08.030.
  5. Miyanaga, A; Hayakawa, Y; Numakura, M; Hashimoto, J; Teruya, K; Hirano, T; Shin-ya, K; Kudo, F; *Eguchi, T, Identification of the Fluvirucin B-2 (Sch 38518) Biosynthetic Gene Cluster from Actinomadura fulva subsp indica ATCC 53714: Substrate Specificity of the β-Amino Acid Selective Adenylating Enzyme FlvN, Biosci. Biotechnol. Biochem., 80, 935–941, 2016, DOI: 10.1080/09168451.2015.1132155.
  6. Kudo, F; Kawamura, K; Furuya, T; Yamanishi, H; Motegi, A; Komatsubara, A; Numakura, M; Miyanaga, A; *Eguchi, T, Parallel Post-Polyketide Synthase Modification Mechanism Involved in FD-891 Biosynthesis in Streptomyces graminofaciens A-8890, ChemBioChem, 17(3), 233–238, 2016, DOI: 10.1002/cbic.201500533.
  7. Kudo, F; Kawamura, K; Uchino, A; Miyanaga, A; Numakura, M; Takayanagi, R; *Eguchi, TGenome Mining of the Hitachimycin Biosynthetic Gene Cluster: Involvement of a Phenylalanine-2,3-aminomutase in Biosynthesis, ChemBioChem, 16(6), 909–914, 2015, DOI: 10.1002/cbic.201500040.
  8. Kudo, F; Miyanaga, A; *Eguchi, T, Biosynthesis of natural products containing β-amino acids, Nat. Prod. Rep., 31(8), 1056–1073, 2014, DOI: 10.1039/c4np00007b.
  9. Miyanaga, A; Cieślak, J; Shinohara, Y; Kudo, F; *Eguchi, T, The Crystal Structure of the Adenylation Enzyme VinN Reveals a Unique β-Amino Acid Recognition Mechanism, J. Biol. Chem., 289(45), 31448–31457, 2014, DOI: 10.1074/jbc.M114.602326.
  10. Takaishi, M; Kudo, F; *Eguchi, T, Identification of the incednine biosynthetic gene cluster: characterization of novel β-glutamate-β-decarboxylase IdnL3, J. Antibiot., 66(12), 691–699, 2013, DOI: 10.1038/ja.2013.76.
  11. 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 the Macrolactam Antibiotic Cremimycin, ChemBioChem, 14(15), 1998–2006, 2013, DOI: 10.1002/cbic.201300370.
  12. 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., 133(45), 18134–18137, 2011, DOI: 10.1021/ja208927r.
  13. Kudo, F; Motegi, A; Mizoue, K; *Eguchi, T, Cloning and Characterization of the Biosynthetic Gene Cluster of 16-Membered Macrolide Antibiotic FD-891: Involvement of a Dual Functional Cytochrome P450 Monooxygenase Catalyzing Epoxidation and Hydroxylation, ChemBioChem, 11(11), 1574–1582, 2010, DOI: 10.1002/cbic.201000214.
  14. Kudo, F; Kitayama, T; Kakinuma, K; *Eguchi, T, Macrolactam formation catalyzed by the thioesterase domain of vicenistatin polyketide synthase, Tetrahedron Lett., 47(10), 1529–1532, 2006, DOI: 10.1016/j.tetlet.2006.01.008.

アミノグリコシド系抗生物質の生合成研究

  1. *Kudo, F; *Eguchi, T, Biosynthesis of cyclitols, Nat. Prod. Rep., 39, 1622-1642, 2022, DOI: 10.1039/d2np00024e.
  2. *Kudo, F; Kitayama, Y; Miyanaga, A; Numakura, M; *Eguchi, T, Stepwise Post-glycosylation Modification of Sugar Moieties in Kanamycin Biosynthesis, ChemBioChem, 22(9), 1668–1675, 2021, DOI: 10.1002/cbic.202000839.
  3. *Kudo, F; Mori, A; Koide, M; Yajima, R; Takeishi, R; Miyanaga, A; *Eguchi, T, One-pot enzymatic synthesis of 2-deoxy-scyllo-inosose from D-glucose and polyphosphate, Biosci. Biotechnol. Biochem., 85(1), 108–114, 2021, DOI: 10.1093/bbb/zbaa025.
  4. *Kudo, F; Kitayama, Y; Miyanaga, A; Hirayama, A; *Eguchi, T, Biochemical and Structural Analysis of a Dehydrogenase, KanD2, and an Aminotransferase, KanS2, That Are Responsible for the Construction of the Kanosamine Moiety in Kanamycin Biosynthesis, Biochemistry, 59(15), 1470–1473, 2020, DOI: 10.1021/acs.biochem.0c00204.
  5. *Kudo, F; Tokumitsu, T; *Eguchi, T, Substrate specificity of radical S-adenosyl-L-methionine dehydratase AprD4 and its partner reductase AprD3 in the C3'-deoxygenation of aminoglycoside antibiotics, J. Antibiot., 70(4), 423–428, 2017, DOI: 10.1038/ja.2016.110.
  6. *Kudo, F; *Eguchi, T, Aminoglycoside Antibiotics: New Insights into the Biosynthetic Machinery of Old Drugs, Chem. Rec., 16(1), 4–18, 2016, DOI: 10.1002/tcr.201500210.
  7. 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, 16(3), 487–495, 2015, DOI: 10.1002/cbic.201402612.
  8. *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., 136(39), 13909–13915, 2014, DOI: 10.1021/ja507759f.
  9. Sucipto, H; Kudo, F; *Eguchi, T, The Last Step of Kanamycin Biosynthesis: Unique Deamination Reaction Catalyzed by the α-Ketoglutarate-Dependent Nonheme Iron Dioxygenase KanJ and the NADPH-Dependent Reductase KanK, Angew. Chem. Int. Ed., 51(14), 3428–3431, 2012, DOI: 10.1002/anie.201108122.
  10. Kudo, F; *Eguchi, T, Biosynthetic genes for aminoglycoside antibiotics, J. Antibiot., 62(9), 471–481, 2009, DOI: 10.1038/ja.2009.76.
  11. Yokoyama, K; Yamamoto, Y; Kudo, F; *Eguchi, T, Involvement of two distinct N-acetylglucosaminyltransferases and a dual-function deacetylase in neomycin biosynthesis, ChemBioChem, 9(6), 865–869, 2008, DOI: 10.1002/cbic.200700717.
  12. Yokoyama, K; Numakura, M; Kudo, F; Ohmori, D; *Eguchi, T, Characterization and mechanistic study of a radical SAM dehydrogenase in the biosynthesis of butirosin, J. Am. Chem. Soc., 129(49), 15147–15155, 2007, DOI: 10.1021/ja072481t.
  13. Kudo, F; Yamamoto, Y; Yokoyama, K; *Eguchi, T; Kakinuma, K, Biosynthesis of 2-deoxystreptamine by three crucial enzymes in Streptomyces fradiae NBRC 12773, J. Antibiot., 58(12), 766–774, 2005, DOI: 10.1038/ja.2005.104.

バクテリオホパンポリオール（BHP）の生合成研究

  1. Sato, S; *Kudo, F; Rohmer, M; *Eguchi, T, Biochemical and Mutational Analysis of Radical S-Adenosyl-L-Methionine Adenosylhopane Synthase HpnH from Zymomonas mobilis Reveals that the Conserved Residue Cysteine-106 Reduces a Radical Intermediate and Determines the Stereochemistry, Biochemistry, 60(38), 2865-2874, 2021, DOI: 10.1021/acs.biochem.1c00536.
  2. Sato, S; *Kudo, F; Rohmer, M; *Eguchi, T, Characterization of Radical SAM Adenosylhopane Synthase, HpnH, which Catalyzes the 5'-Deoxyadenosyl Radical Addition to Diploptene in the Biosynthesis of C-35 Bacteriohopanepolyols, Angew. Chem. Int. Ed., 59, 237–241, 2020, DOI: 10.1002/anie.201911584.

その他の代謝産物

  1. *Kudo, F; Chikuma, T; Nambu, M; Chisuga, T; Sumimoto, S; Iwasaki, A; Suenaga, K; Miyanaga, A; *Eguchi, T, Unique Initiation and Termination Mechanisms Involved in the Biosynthesis of a Hybrid Polyketide-Nonribosomal Peptide Lyngbyapeptin B Produced by the Marine Cyanobacterium Moorena bouillonii, ACS Chem. Biol., 18(4), 875-883, 2023, DOI: 10.1021/acschembio.3c00011.
  2. Amagai, K; Ikeda, H; Hashimoto, J; Kozone, I; Izumikawa, M; Kudo, F; Eguchi, T; Nakamura, T; Osada, H; *Takahashi, S; *Shin-ya, K, Identification of a gene cluster for telomestatin biosynthesis and heterologous expression using a specific promoter in a clean host, Sci. Rep., 7, 3382, 2017, DOI: 10.1038/s41598-017-03308-5.
  3. *Kudo, F; Tsunoda, T; Takashima, M; *Eguchi, T, Five-Membered Cyclitol Phosphate Formation by a myo-Inositol Phosphate Synthase Orthologue in the Biosynthesis of the Carbocyclic Nucleoside Antibiotic Aristeromycin, ChemBioChem, 17(22), 2143–2148, 2016, DOI: 10.1002/cbic.201600348.
  4. *Kudo, F; Matsuura, Y; Hayashi, T; Fukushima, M; *Eguchi, T, Genome mining of the sordarin biosynthetic gene cluster from Sordaria araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and GDP-6-deoxyaltrose transferase, J. Antibiot., 69(7), 541–548, 2016, DOI: 10.1038/ja.2016.40.
  5. Kudo, F; Yonezawa, T; Komatsubara, A; Mizoue, K; *Eguchi, T, Cloning of the biosynthetic gene cluster for naphthoxanthene antibiotic FD-594 from Streptomyces sp TA-0256, J. Antibiot., 64(1), 123–132, 2011, DOI: 10.1038/ja.2010.145.
  6. *Kudo, F; Kasama, Y; Hirayama, T; *Eguchi, T, Cloning of the pactamycin biosynthetic gene cluster and characterization of a crucial glycosyltransferase prior to a unique cyclopentane ring formation, J. Antibiot., 60(8), 492–503, 2007, DOI: 10.1038/ja.2007.63.

酵素の精密機能解析

  1. *Kudo, F; Minato, A; Sato, S; Nagano, N; Maruyama, C; Hamano, Y. Hashimoto, J; Kozone, I; Shin-ya, K; *Eguchi, T, Mechanism of S-Adenosyl-L-methionine C-Methylation by Cobalamin-dependent Radical S-Adenosyl-L-methionine Methylase in 1-Amino-2-methylcyclopropanecarboxylic Acid Biosynthesis, Org. Lett., 24(49), 8975-8979, 2022, DOI: 10.1021/acs.orglett.2c03555.
  2. Chisuga, T; Nagai, A; *Miyanaga, A; Goto, E; Kishikawa, K; Kudo, F; *Eguchi, T., Structural Insight into the Reaction Mechanism of Ketosynthase Like Decarboxylase in a Loading Module of Modular Polyketide Synthases, ACS Chem. Biol., 17(1), 198-206, 2022, DOI: 10.1021/acschembio.1c00856.
  3. *Miyanaga, A; Kudo, F; Eguchi, T, Recent advances in the structural analysis of adenylation domains in natural product biosynthesis, Curr. Opin. Chem. Biol., 71, e102212, 2022, DOI: 10.1016/j.cbpa.2022.102212.
  4. *Kudo, F; Miyanaga, A; *Eguchi, T, Structural basis of the nonribosomal codes for nonproteinogenic amino acid selective adenylation enzymes in the biosynthesis of natural products, J. Ind. Microbiol. Biotechnol., 46(3-4), 515–536, 2019, DOI: 10.1007/s10295-018-2084-7.
  5. *Kudo, F; Tsunoda, T; Yamaguchi, K; Miyanaga, A; *Eguchi, T, Stereochemistry in the Reaction of the myo-Inositol Phosphate Synthase Ortholog Ari2 during Aristeromycin Biosynthesis, Biochemistry, 58(51), 5112–5116, 2019, DOI: 10.1021/acs.biochem.9b00981.
  6. Sato, S; *Kudo, F; Kuzuyama, T; Hammerschmidt, F; *Eguchi, T, C-Methylation Catalyzed by Fom3, a Cobalamin-Dependent Radical S-adenosyl-L-methionine Enzyme in Fosfomycin Biosynthesis, Proceeds with Inversion of Configuration, Biochemistry, 57(33), 4963–4966, 2018, DOI: 10.1021/acs.biochem.8b00614.
  7. Sato, S; *Kudo, F; Kim, SY; Kuzuyama, T; *Eguchi, T, Methylcobalamin-Dependent Radical SAM C-Methyltransferase Fom3 Recognizes Cytidylyl-2-hydroxyethylphosphonate and Catalyzes the Nonstereoselective C-Methylation in Fosfomycin Biosynthesis, Biochemistry, 56(28), 3519–3522, 2017, DOI: 10.1021/acs.biochem.7b00472.
  8. Cieślak, J; *Miyanaga, A; Takaku, R; Takaishi, M; Amagai, K; Kudo, F; *Eguchi, T, Biochemical characterization and structural insight into aliphatic β-amino acid adenylation enzymes IdnL1 and CmiS6, Proteins, 85(7), 1238–1247, 2017, DOI: 10.1002/prot.25284.
  9. Chisuga, T; Miyanaga, A; Kudo, F; *Eguchi, T, Structural analysis of the dual-function thioesterase SAV606 unravels the mechanism of Michael addition of glycine to an α,β-unsaturated thioester, J. Biol. Chem., 292(26), 10926–10937, 2017, DOI: 10.1074/jbc.M117.792549.
  10. Hirayama, A; Miyanaga, A; *Kudo, F; *Eguchi, T, Mechanism-Based Trapping of the Quinonoid Intermediate by Using the K276R Mutant of PLP-Dependent 3-Aminobenzoate Synthase PctV in the Biosynthesis of Pactamycin, ChemBioChem, 16(17), 2484–2490, 2015, DOI: 10.1002/cbic.201500426.
  11. 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., 588(6), 995–1000, 2014, DOI: 10.1016/j.febslet.2014.01.060.

タンパク質間相互作用に関する研究

  1. *Miyanaga, A; Nagata, K; Nakajima, J; Chisuga, T; Kudo, F; *Eguchi, T, Structural Basis of Amide-Forming Adenylation Enzyme VinM in Vicenistatin Biosynthesis, ACS Chem. Biol., 18(11), 2343-2348, 2023, DOI: 10.1021/acschembio.3c00517.
  2. Chisuga, T; Murakami, S; *Miyanaga, A; Kudo, F; *Eguchi, T, Structure-Based Analysis of Transient Interactions between Ketosynthase-like Decarboxylase and Acyl Carrier Protein in a Loading Module of Modular Polyketide Synthase, ACS Chem. Biol., 18(6), 1398-1404, 2023, DOI: 10.1021/acschembio.3c00151.
  3. *Miyanaga, A; Kawada, K; Chisuga, T; Kudo, F; *Eguchi, T, Structural Basis of Transient Interactions of Acyltransferase VinK with the Loading Acyl Carrier Protein of the Vicenistatin Modular Polyketide Synthase, Biochemistry, 62(1), 17-21, 2023, DOI: 10.1021/acs.biochem.2c00645.
  4. *Miyanaga, A; Ouchi, R; Kudo, F; *Eguchi, T, Complex structure of the acyltransferase VinK and the carrier protein VinL with a pantetheine cross-linking probe, Acta Crystallographica Section F, 77, 294-302, 2021, DOI: 10.1107/S2053230X21008761.
  5. *Miyanaga, A; Kurihara, S; Chisuga, T; Kudo, F; *Eguchi, T, Structural Characterization of Complex of Adenylation Domain and Carrier Protein by Using Pantetheine Cross-Linking Probe, ACS Chem. Biol., 15(7), 1808–1812, 2020, DOI: 10.1021/acschembio.0c00403.
  6. *Miyanaga, A; Kudo, F; *Eguchi, T, Protein-protein interactions in polyketide synthase-nonribosomal peptide synthetase hybrid assembly lines, Nat. Prod. Rep., 35(11), 1185–1209, 2018, DOI: 10.1039/c8np00022k.
  7. *Miyanaga, A; Ouchi, R; Ishikawa, F; Goto, E; Tanabe, G; Kudo, F; *Eguchi, T, Structural Basis of Protein-Protein Interactions between a trans-Acting Acyltransferase and Acyl Carrier Protein in Polyketide Disorazole Biosynthesis, J. Am. Chem. Soc., 140(25), 7970–7978, 2018, DOI: 10.1021/jacs.8b04162.
  8. *Miyanaga, A; Iwasawa, S; Shinohara, Y; Kudo, F; *Eguchi, T, Structure-based analysis of the molecular interactions between acyltransferase and acyl carrier protein in vicenistatin biosynthesis, Proc. Natl. Acad. Sci. U. S. A., 113(7), 1802–1807, 2016, DOI: 10.1073/pnas.1520042113.

学生、ポスドク時代の主論文

ポスドク時代の論文（β-ラクタム合成酵素に関する研究）

  1. Labonte, JW; Kudo, F; Freeman, MF; Raber, ML; *Townsend, CA, Engineering the synthetic potential of β-lactam synthetase and the importance of catalytic loop dynamics, MedChemComm, 3(8), 960–966, 2012, DOI: 10.1039/c2md00305h.

ポスドク時代の論文（DEBSに関する研究）

  1. *Cane, DE; Kudo, F; Kinoshita, K; Khosla, C, Precursor-directed biosynthesis: Biochemical basis of the remarkable selectivity of the erythromycin polyketide synthase toward unsaturated triketides, Chem. Biol., 9(1), 131–142, 2002, DOI: 10.1016/S1074-5521(02)00089-3.
  2. Wu, N; Kudo, F; Cane, DE; *Khosla, C, Analysis of the molecular recognition features of individual modules derived from the erythromycin polyketide synthase, J. Am. Chem. Soc., 122(20), 4847–4852, 2000, DOI: 10.1021/ja000023d

学生時代の論文（2-デオキシ-scyllo-イノソース合成酵素に関する研究）

  1. Ota, Y; Tamegai, H; Kudo, F; Kuriki, H; Koike-Takeshita, A; Eguchi, T; *Kakinuma, K,, Butirosin-biosynthetic gene cluster from Bacillus circulans, J. Antibiot., 53(10), 1158–1167, 2000, DOI: 10.7164/antibiotics.53.1158.
  2. *Kakinuma, K; Nango, E; Kudo, F; Matsushima, Y; Eguchi, T, An expeditious chemo-enzymatic route from glucose to catechol by the use of 2-deoxy-scyllo-inosose synthase, Tetrahedron Lett., 41(12), 1935–1938, 2000, DOI: 10.1016/S0040-4039(00)00064-2.
  3. Kudo, F; Tamegai, H; Fujiwara, T; Tagami, U; Hirayama, K; *Kakinuma, K, Molecular cloning of the gene for the key carbocycle-forming enzyme in the biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics and its comparison with dehydroquinate synthase, J. Antibiot., 52(6), 559–571, 1999, DOI: 10.7164/antibiotics.52.559.
  4. Kudo, F; Hosomi, Y; Tamegai, H; *Kakinuma, K, Purification and characterization of 2-deoxy-scyllo-inosose synthase derived from Bacillus circulans. A crucial carbocyclization enzyme in the biosynthesis of 2-deoxystreptarnine-containing aminoglycoside antibiotics, J. Antibiot., 52(2), 81–88, 1999, DOI: 10.7164/antibiotics.52.81.
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