Leading-edge Biotechnology Research Group

Research Project

Natural product library has been applied for drug development, therefore more than 60 percent of the clinical drugs are originated from natural compounds. Pharmaceutical companies provided their natural product library establishing World-largest natural library in our laboratory. We are developing wide range of drug screening for clinical drugs, animal drugs, agricultural chemicals, etc., on various drug targets provided by not only industrial companies but also basic research academia.

Research Project

Recent studies revealed that human beings can draw only 1/3 of total ability of the natural compound production by conventional fermentation technology. Our research program targets the development of the next-generation natural compound production technology which leads the production of novel compounds by heterologous expression system applying on cryptic biosynthetic genes. In addition, we perform natural compounds with complex structures which is essential for fine tunings in the drug developments such as improvement of pharmacokinetics, avoidance of side effects and so on. By employing these techniques, we contribute to drug developments.

Research Project

Natural products are an essential resource of bioactive compounds for developing medicines. Such natural products of highly complex structures are challenging to derivatize even by current organic chemistry, so a new methodology is necessary. Recently, we established a genetic engineering technique (in vitro module editing) capable of precisely manipulating the biosynthetic genes for "polyketides." Since the genes encoding polyketide synthase consist of multiple and highly similar sequences, a precise modification was impossible with a conventional recombination-based technique. Our new method makes genetic insertion, replacement, and deletion consistent with the design. It leads to the production of new polyketides.Based on this technology, we are committing to a burst increment of polyketide diversity (combinatorial biosynthesis), fusing natural products with new medical modalities, developing high-valued compounds for stimulating bio-production society, and so on.

Research Project

Dynamic cellular events beyond genetic encodings, such as epigenetics, and the formation of membraneless organelles, play critical roles in dictating cellular functions. Taking advantage of technologies such as i) live imaging of epigenetic state, using the Momiji system, and ii) Integrated human full-length cDNA clone database that covers 80% of the human proteome and contains their localization information, we study the dynamics of cell state and promote research that will lead to the understanding of organisms and drug discovery.　 Specifically, our research focuses on "X chromosome inactivation" in mammals and "non-membrane structures" in the nucleus of mammals.

Results

• Koshiguchi, M; Yonezawa, N; Hatano, Y; Suenaga, H; Yamagata, K; Kobayashi, S.
  A system to analyze the initiation of random X-chromosome inactivation using time-lapse imaging of single cells.
  SCI REP. 2024 Sep 2;14(1):20327. doi: 10.1038/s41598-024-71105-y
• Nishimura, T; Kudo, K; Izumikawa, M; Kozone, I; Hashimoto, J; Kagaya, N; Suenaga, H; Takeuchi, K; Shin-Ya, K.
  Isolation and Structure Elucidation of JBIR-157, a Skeletally Novel Aromatic Polyketide Produced by the Heterologous Expression of a Cryptic Gene Cluster.
  CHEM PHARM BULL (Tokyo). 2024;72(5):475-479. doi: 10.1248/cpb.c24-00144
• Song, X; Nihashi, Y; Imai, Y; Mori, N; Kagaya, N; Suenaga, H; Shin-Ya, K; Yamamoto, M; Setoyama, D; Kunisaki Y; Kida, YS.
  Collagen Lattice Model, Populated with Heterogeneous Cancer-Associated Fibroblasts, Facilitates Advanced Reconstruction of Pancreatic Cancer Microenvironment.
  INT J MOL SCI. 2024 Mar 27;25(7):3740. doi: 10.3390/ijms25073740
• Kudo, K; Nishimura, T; Izumikawa, M; Kozone, I; Hashimoto, J; Fujie, M; Suenaga, H; Ikeda, H; Satoh, N; Shin-Ya, K.
  Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds.
  J ANTIBIOT (Tokyo). 2024 Mar 4. doi: 10.1038/s41429-024-00711-9
• Hashimoto, T; Suenaga, H; Amagai, K; Hashimoto, J; Kozone, I; Takahashi, S; Shin-Ya, K.
  In Vitro Module Editing Of NRPS Enables Production Of Highly Potent Gq-Signaling Inhibitor FR900359 Derived From Unculturable Plant Symbiont.
  ANGEW CHEM INT ED ENGL. 2024 Jan 18:e202317805. doi: 10.1002/anie.202317805
• Suzuki, S; Saito, S; Narushima, Y; Kodani, S; Kagaya, N; Suenaga, H; Shin-Ya, K; Arai, MA.
  Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation.
  J ANTIBIOT (Tokyo). 2023 Nov 8. doi: 10.1038/s41429-023-00673-4
• Fujihara, H; Hirose, J; Suenaga, H.
  Evolution of genetic architecture and gene regulation in biphenyl/PCB-degrading bacteria.
  FRONTIERS IN MICROBIOLOGY. 2023 Jun 7;14:1168246. doi: 10.3389/fmicb.2023.1168246
• Arima, K; Akiyama, S; Shin-Ya, K; Matsuda, K; Wakimoto, T.
  Carrier Protein Mediated Formation of the Dihydropyridazinone Ring in Actinopyridazinone Biosynthesis.
  ANGEW CHEM INT ED ENGL. 2023 May 17:e202305155. doi: 10.1002/anie.202305155
• 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. 2023 Jan 5. doi: 10.1002/cbic.202200670
• 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. 2022 Dec 2. doi: 10.1021/acs.orglett.2c03555
• Sugio, Y; Yamagami, R; Shigi, N; Hori, H.
  A selective and sensitive detection system for 4-thiouridine modification in RNA.
  RNA. 2022 Nov 21:rna.079445.122. doi: 10.1261/rna.079445.122
• Kawai, S; Hagihara, R; Shin-Ya, K; Katsuyama, Y; Ohnishi, Y.
  Bacterial Avenalumic Acid Biosynthesis Includes Substitution of an Aromatic Amino Group for Hydride by Nitrous Acid Dependent Diazotization.
  ANGEW CHEM INT ED ENGL. 2022 Sep 17. doi: 110.1002/anie.202211728
• Choirunnisa, AR; Arima, K; Abe,Y; Kagaya, K; Kudo, K; Suenaga, H; Hashimoto, J; Fujie, M; Satoh, N; Shin-Ya, K; Matsuda, K; Wakimoto, T.
  New azodyrecins identified by a genome mining-directed reactivity-based screening.
  BEILSTEIN J ORG CHEM. 2022 Aug 10;18:1017-1025. doi: 10.3762/bjoc.18.102
• Matsuda, K; Arima, K; Akiyama, S; Yamada, Y; Abe, Y; Suenaga, H; Hashimoto, J; Shin-Ya, K; Nishiyama, M; Wakimoto, T.
  A Natural Dihydropyridazinone Scaffold Generated from a Unique Substrate for a Hydrazine-Forming Enzyme.
  J AM CHEM SOC. 2022 Jun 30. doi: 10.1021/jacs.2c05269
• Yamamoto, K; Takahashi, K; OConnor, SE; Mimura, T.
  Imaging MS Analysis in Catharanthus roseus.
  METHODS MOL BIOL. 2022;2505:33-43. doi: 10.1007/978-1-0716-2349-7_2
• Sasaki, K; Suzuki, M; Sonoda, T; Schneider-Poetsch, T; Ito, A; Takagi, M; Fujishiro, S; Sohtome, Y; Dodo, K; Umehara, T; Aburatani, H; Shin-Ya, K; Nakao, Y; Sodeoka, M; Yoshida, M.
  Visualization of the dynamic interaction between nucleosomal histone H3K9 tri-methylation and HP1α chromodomain in living cells.
  CELL CHEM BIOL. 2022 Jun 18:S2451-9456(22)00198-2. doi: 10.1016/j.chembiol.2022.05.006
• Kojima, S; Shiochi, N; Sato, K; Yamaura, M; Ito, T; Yamamura, N; Goto, N; Odamoto, M; Kobayashi, S; Kimura, T; Sekita, Y.
  Epigenome editing reveals core DNA methylation for imprinting control in the Dlk1-Dio3 imprinted domain.
  NUCLEIC ACIDS RESEARCH. 2022 May 11. doi: 10.1093/nar/gkac344
• Demachi, A; Ohte, S; Uchida, R; Shin-Ya, K;Ohshiro, T; Tomoda, H; Ikeda, H.
  Discovery of prescopranone, a key intermediate in scopranone biosynthesis.
  JOURNAL OF ANTIBIOTICS. 2022 Apr 20. doi: 10.1038/s41429-022-00521-x
• Rider, SD Jr; Gadgil, RY; Hitch, DC; Damewood, FJ 4th; Zavada, N; Shanahan, M; Alhawach, V; Shrestha, R; Shin-Ya, K; Leffak, M.
  Stable G-quadruplex DNA structures promote replication-dependent genome instability.
  J BIOL CHEM. 2022 Apr 18:101947. doi: 10.1016/j.jbc.2022.101947
• Suenaga, H; Matsuzawa, T; Sahara, T.
  Discovery by metagenomics of a functional tandem repeat sequence that controls gene expression in bacteria.
  FEMS MICROBIOL ECOL. 2022 Mar 28:fiac037. doi: 10.1093/femsec/fiac037
• Nagata, R; Suemune, H; Kobayashi, M; Shinada, T; Shin-Ya, K; Nishiyama, M; Hino, T; Sato, Y; Kuzuyama, T; Nagano, S.
  Structural Basis for the Prenylation Reaction of Carbazole-Containing Natural Products Catalyzed by Squalene Synthase-like Enzymes.
  ANGEW CHEM INT ED ENGL. 2022 Mar 2. doi: 10.1002/anie.202117430
• Yamamoto, K; Yoneda, Y; Makino, A; Tanaka, Y; Meng, XY; Hashimoto, J; Shin-Ya, K; Satoh, N; Fujie, M; Toyama, T; Mori, K; Ike, M, Morikawa, M; Kamagata, Y; Tamaki, H.
  Draft Genome Sequence of Bryobacteraceae Strain F-183.
  MICROBIOL RESOUR ANNOUNC. 2022 Jan 13:e0045321. doi: 10.1128/mra.00453-21
• Hirose, J; Watanabe, T; Futagami, T; Fujihara, H; Kimura, N; Suenaga, H; Goto, M; Suyama, A; Furukawa, K.
  A New ICEclc Subfamily Integrative and Conjugative Element Responsible for Horizontal Transfer of Biphenyl and Salicylic Acid Catabolic Pathway in the PCB-Degrading Strain Pseudomonas stutzeri KF716.
  MICROORGANISMS. 2021 Nov 29;9(12):2462. doi: 10.3390/microorganisms9122462
• Shigi, N.
  Biosynthesis and Degradation of Sulfur Modifications in tRNAs.
  INT J MOL SCI. 2021 Nov 3;22(21):11937. doi: 10.3390/ijms222111937
• Tsutsumi, H; Moriwaki, Y; Terada, T; Shimizu, K; Shin-Ya, K; Katsuyama, Y; Ohnishi, Y.
  Structural and Molecular Basis of the Catalytic Mechanism of Geranyl Pyrophosphate C-6 Methyltransferase: Creation of an Unprecedented Farnesyl Pyrophosphate C-6 Methyltransferase.
  ANGEW CHEM INT ED ENGL. 2021 Oct 9. doi: 10.1002/anie.202111217
• Suenaga, H; Kagaya, N; Kawada, M; Tatsuda, D; Sato, T; Shin-Ya, K.
  Phenotypic screening system using three-dimensional (3D) culture models for natural product screening.
  J ANTIBIOT (Tokyo). 2021 Jul 29. doi: 10.1038/s41429-021-00457-8
• Seimiya, H; Nagasawa, K; Shin-Ya, K.
  Chemical targeting of G-quadruplexes in telomeres and beyond for molecular cancer therapeutics.
  J ANTIBIOT (Tokyo). 2021 Jul 20. doi: 10.1038/s41429-021-00454-x
• Yoneda, Y; Yamamoto, K; Makino, A; Tanaka, Y; Meng, XY; Hashimoto, J; Shin-Ya, K; Satoh, N; Fujie, M; Toyama, T; Mori, K; Ike, M; Morikawa, M; Kamagata, Y; Tamaki, H
  Novel Plant-Associated Acidobacteria Promotes Growth of Common Floating Aquatic Plants, Duckweeds
  Microorganisms. 2021 May 24;9(6):1133. doi: 10.3390/microorganisms9061133
• Nishimura, T; Kawahara, T; Kagaya, N; Ogura, Y; Takikawa, H; Suenaga, H; Adachi, M; Hirokawa, T; Doi, T; Shin-Ya, K.
  JBIR-155, a Specific Class D β-Lactamase Inhibitor of Microbial Origin.
  ORG LETT. 2021 May 24. doi: 10.1021/acs.orglett.1c01352
• Kudo, K; Nishimura, T; Kozone, I; Hashimoto, J; Kagaya, N; Suenaga, H; Ikeda, H; Shin-Ya, K.
  Hemiacetal-less rapamycin derivatives designed and produced by genetic engineering of a type I polyketide synthase.
  SCI REP. 2021 May 11;11(1):9944. doi: 10.1038/s41598-021-88583-z
• Liu, C; Hashimoto, J; Kudo, K; Shin-Ya, K; Kakeya, H.
  An Atypical Arginine Dihydrolase Involved in the Biosynthesis of Cyclic Hexapeptide Longicatenamides.
  CHEM ASIAN J. 2021 Apr 22. doi: 10.1002/asia.202100181
• Okubo, S; Ena, E; Okuda, A; Kozone, I; Hashimoto, J; Nishitsuji, Y; Fujie, M; Satoh, N; Ikeda, H; Shin-Ya, K.
  Identification of functional cytochrome P450 and ferredoxin from Streptomyces sp. EAS-AB2608 by transcriptional analysis and their heterologous expression.
  APPL MICROBIOL BIOTECHNOL. 2021 May 4. doi: 10.1007/s00253-021-11304-z
• Katsuyama, Y; Sone, K; Harada, A; Kawai, S; Urano, N; Adachi, N; Moriya, T; Kawasaki, M; Shin-Ya, K; Senda, T; Ohnishi, Y
  Structural and functional analyses of the tridomain-nonribosomal peptide synthetase FmoA3 for 4-methyloxazoline ring formation
  Angew Chem Int Ed Engl. 2021 Mar 29. doi: 10.1002/anie.202102760
• Okabe S, Shin-ya K, Dan S, Nagasawa K, Seimiya H
  Establishment of G-quadruplex ligand-resistant cancer cells and elucidation of the resistance mechanism.
  CANCER SCIENCE 112 558-558; FEB
• Miyazaki K, Suenaga H, Oshiki M, Kawano S, Fukushima T
  Complete Genome Sequence of Thiohalobacter sp. Strain COW1, Isolated from Activated Sludge Treating Coke Oven Wastewater.
  MICROBIOL RESOUR ANNOUNC. 2021 Feb 18;10(7):e00013-21. doi: 10.1128/MRA.00013-21
• Ueoka R, Hashimoto J, Kozone I, Hashimoto T, Kudo K, Kagaya N, Suenaga H, Ikeda H, Shin-Ya K
  A novel methymycin analog, 12-ketomethymycin N-oxide, produced by the heterologous expression of the large pikromycin/methymycin biosynthetic gene cluster of Streptomyces sp. AM4900.
  BIOSCI BIOTECHNOL BIOCHEM. 2020 Dec 22:zbaa111. doi: 10.1093/bbb/zbaa111
• Hashimoto T, Hashimoto J, Kagaya N, Nishimura T, Suenaga H, Nishiyama M, Kuzuyama T, Shin-Ya K
  A novel oxazole-containing tetraene compound, JBIR-159, produced by heterologous expression of the cryptic trans-AT type polyketide synthase biosynthetic gene cluster.
  J ANTIBIOT (Tokyo). 2021 Feb 8. doi: 10.1038/s41429-021-00410-9
• Khaledian B, Taguchi A, Shin-Ya K, Kondo-Ida L, Kagaya N, Suzuki M, Kajino T, Yamaguchi T, Shimada Y, Takahashi T
  Inhibition of HSP90 destabilizes receptor tyrosine kinase ROR1 in lung adenocarcinoma.
  CANCER SCI. 2020 Dec 28. doi: 10.1111/cas.14786
• Nogawa T, Terai A, Amagai K, Hashimoto J, Futamura Y, Okano A, Fujie M, Satoh N, Ikeda H, Shin-Ya K, Osada H, Takahashi S
  Heterologous Expression of the Biosynthetic Gene Cluster for Verticilactam and Identification of Analogues
  J Nat Prod. 2020 Nov 20. doi: 10.1021/acs.jnatprod.0c00755
• Ueoka R, Shinzato N, Kagaya N, Suenaga H, Shin-Ya K
  Pseudoalteropeptide A, a novel lipopeptide from the marine bacterium Pseudoalteromonas piscicida SWA4_PA4 isolated from marine seaweed
  J Antibiot (Tokyo). 2020 Oct 15. (2020) doi: 10.1038/s41429-020-00377-z
• Bastola S, Pavlyukov MS, Yamashita D, Ghosh S, Cho H, Kagaya N, Zhang Z, Minata M, Lee Y, Sadahiro H, Yamaguchi S, Komarova S, Yang E, Markert J, Nabors LB, Bhat K, Lee J, Chen Q, Crossman DK, Shin-Ya K, Nam DH, Nakano I
  Glioma-initiating cells at tumor edge gain signals from tumor core cells to promote their malignancy
  Nat Commun. 11(1):4660. (2020) doi: 10.1038/s41467-020-18189-y
• Gadgil RY, Romer EJ, Goodman CC, Rider SD Jr, Damewood FJ 4th, Barthelemy JR, Shin-Ya K, Hanenberg H, Leffak M.
  Replication stress at microsatellites causes DNA double strand breaks and break induced replication.
  J BIOL CHEM jbc.RA120.013495. (2020) doi: 10.1074/jbc.RA120.013495
• Jo T, Nishikori M, Kogure Y, Arima H, Sasaki, K; Sasaki Y, Nakagawa T, Iwai F, Momose S; Shiraishi A; Kiyonari H, Kagaya N, Onuki T, Shin-ya K, Yoshida M, Kataoka K, Ogawa S, Iwai K, Takaori-Kondo A
  LUBAC accelerates B-cell lymphomagenesis by conferring resistance to genotoxic stress on B cells
  BLOOD 136 (6) :684-697 (2020) doi: 10.1182/blood.2019002654
• Hayakawa Y, Yoshida T, Kimata S,Shin-Ya K
  Dunaimycin C3, a new GRP78 downregulator fromStreptomyces sp. RAN389
  J. Antibiotics　32: 0 (2020) doi: 10.1038/s41429-020-0356-8
• Kataura T, Tashiro E, Nishikawa S, Shibahara K, Muraoka Y, Miura M, Sakai S, Katoh N, Totsuka M, Onodera M,Shin-Ya K,Miyamoto K, Sasazawa Y, Hattori N, Saiki S, Imoto M
  A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers
  AUTOPHAGY; Aug　7;1-17 (2020) doi: 10.1080/15548627.2020.1794590
• Kudo K,Hashimoto T,Hashimoto J, Kozone I, Kagaya N,Ueoka R,Nishimura T, Komatsu M,Suenaga H,Ikeda H,Shin-Ya K
  In vitro Cas9-assisted editing of modular polyketide synthase genes to produce desired natural product derivatives
  Nat Commun.　11:4022. (2020) doi: 10.1038/s41467-020-17769-2
• Hayakawa Y, Yaguchi R, Akimoto M, Kimata S, Shin-Ya K
  Neocurromycin A, a new GRP78 downregulator from Streptomyces sp. RAI364
  J Antibiot　0: 0 (2020) doi: 10.1038/s41429-020-0339-9
• Kurosawa S, Matsuda K, Hasebe F, Shiraishi T, Shin-Ya K, Kuzuyama T, Nishiyama M
  Guanidyl modification of the 1-azabicyclo[3.1.0]hexane ring in ficellomycin essential for its biological activity
  Org Biomol Chem. 25: 0 (2020) doi: 10.1039/d0ob00339e
• Hashimoto T, Kozone I, Hashimoto J, Suenaga H, Fujie M, Satoh N, Ikeda H, Shin-Ya K
  Identification, Cloning and Heterologous Expression of Biosynthetic Gene Cluster for Desertomycin
  J Antibiot. (2020) doi: 10.1038/s41429-020-0319-0
• Maruyama C, Chinone Y, Sato S, Kudo F, Ohsawa K, Kubota J, Hashimoto J, Kozone I, Doi T, Shin-Ya K, Eguchi T, Hamano Y
  C-Methylation of S-adenosyl-L-Methionine Occurs Prior to Cyclopropanation in the Biosynthesis of 1-Amino-2-Methylcyclopropanecarboxylic Acid (Norcoronamic Acid) in a Bacterium
  Biomolecules 10: E775 (2020) doi: 10.3390/biom10050775
• Jo T, Nishikori M, Kogure Y, Arima H, Sasaki K, Sasaki Y, Nakagawa T, Iwai F, Momose S, Shiraishi A, Kiyonari H, Kagaya N, Onuki T, Shin-Ya K, Yoshida M, Kataoka K, Ogawa S, Iwai K, Takaori-Kondo A.
  LUBAC Accelerates B-cell Lymphomagenesis by Conferring B Cells Resistance to Genotoxic Stress
  Blood (2020) doi: 10.1182/blood.2019002654
• Kawahara T, Itoh M, Izumikawa M, Kagaya N, Sakata N, Tsuchida T, Shin-Ya K
  New phenylspirodrimane metabolites MBJ-0030, MBJ-0031, and MBJ-0032 isolated from the soil fungal strain Stachybotrys sp. f23793
  Biosci Biotechnol Biochem.(2020) doi: 10.1080/09168451.2020.1757402
• Chen MH, Ishizaka M, Narai S, Horitani M, Shigi N, Yao M, Tanaka Y
  The [4Fe-4S] cluster of sulfurtransferase TtuA desulfurizes TtuB during tRNA modification in Thermus thermophilus
  Commun Biol. 3: 168 (2020) doi: 10.1038/s42003-020-0895-3
• Shigi N, Horitani M, Miyauchi K, Suzuki T, Kuroki M
  An ancient type of MnmA protein is an iron-sulfur cluster-dependent sulfurtransferase for tRNA anticodons
  RNA 26: 240-250 (2020) doi: 10.1261/rna.072066.119
• Hashimoto T, Kozone I, Hashimoto J, Ueoka R, Kagaya N, Fujie M, Sato N, Ikeda H, Shin-ya K
  Novel macrolactam compound produced by the heterologous expression of a large cryptic biosynthetic gene cluster of Streptomyces rochei IFO12908
  J Antibiot. 73: 171-174 (2020) doi: 10.1038/s41429-019-0265-x
• Demachi A, Uchida R, Arima S, Nagamitsu T, Hashimoto J, Komatsu M, Kozone I, Shin-Ya K, Tomoda H, Ikeda H
  An Unusual Extender Unit Is Incorporated into the Modular Polyketide Synthase of Scopranones Biosynthesis
  Biochem. 58: 5066-5073 (2019) doi: 10.1021/acs.biochem.9b00908
• Yamamoto K, Takahashi K, Caputi L, Mizuno H, Rodriguez-Lopez CE, Iwasaki T, Ishizaki K, Fukaki H, Ohnishi M, Yamazaki M, Masujima T, OConnor SE, Mimura T
  The complexity of intercellular localisation of alkaloids revealed by single-cell metabolomics
  New Phytol. 224: 848-859 (2019) doi: 10.1111/nph.16138
• Romo AJ, Shiraishi T, Ikeuchi H, Lin GM, Geng YJ, Lee YH, Liem, PH, Ma TL, Ogasawara Y, Shin-Ya K, Nishiyama M, Kuzuyama T, Liu HW
  The Amipurimycin and Miharamycin Biosynthetic Gene Clusters: Unraveling the Origins of 2-Aminopurinyl Peptidyl Nucleoside Antibiotics
  J Am Chem Soc. 141: 14152-14159 (2019) doi: 10.1021/jacs.9b03021
• Takase S, Kurokawa R, Kondoh Y, Honda K, Suzuki T, Kawahara T, Ikeda H, Dohmae N, Osada H, Shin-Ya K, Kushiro T, Yoshida M, Matsumoto K
  Mechanism of Action of Prethioviridamide, an Anticancer Ribosomally Synthesized and Post-Translationally Modified Peptide with a Polythioamide Structure
  ACS Chem Biol. 14: 1819-1828 (2019) doi: 10.1021/acschembio.9b00410
• Murashima A, Shinjo K, Katsushima K, Onuki T, Kondoh Y, Osada H, Kagaya N, Shin-ya K, Kimura H, Yoshida M, Murakami S, Kondo Y
  Identification of a chemical modulator of EZH2-mediated silencing by cell-based high-throughput screening assay
  J Biochem. 166: 41-50 (2019) doi: 10.1093/jb/mvz007
• Kudo K, Koiwai H, Kagaya N, Nishiyama M, Kuzuyama T, Shin-Ya K, Ikeda H
  Comprehensive Derivatization of Thioviridamides by Heterologous Expression
  ACS Chem Biol.14: 1135-1140 (2019) doi: 10.1021/acschembio.9b00330
• Hirose J, Fujihara H, Watanabe T, Kimura N, Suenaga H, Futagami T, Goto M, Suyama A, Furukawa K
  Biphenyl/PCB Degrading bph Genes of Ten Bacterial Strains Isolated from Biphenyl-Contaminated Soil in Kitakyushu, Japan: Comparative and Dynamic Features as Integrative Conjugative Elements (ICEs)
  Genes 10: 10 (2019) doi: 10.3390/genes10050404
• Kobayashi M, Tomita T, Shin-ya K, Nishiyama M, Kuzuyama T
  An Unprecedented Cyclization Mechanism in the Biosynthesis of Carbazole Alkaloids in Streptomyces
  Angew Chem Int Ed Engl. 189: 233-248 (2019) doi: 10.1002/anie.201906864
• Oda S, Nomura S, Nakagawa M, Shin-Ya K, Kagaya N, Kawahara T
  Solid-liquid Interface Screening SystemApplication to the Screening of Antibiotic and Cytotoxic Substance-producing Fungi
  Biocontrol Sci. 24: 47-56 (2019) doi: 10.4265/bio.24.47
• Xiao A, Brenneman B, Floyd D, Comeau L, Spurio K, Olmez I, Lee J, Nakano I, Godlewski J, Bronisz A, Kagaya N, Shin-Ya K, Purow B
  Statins affect human glioblastoma and other cancers through TGF-beta inhibition
  Oncotarget 10: 1716-1728 (2019) doi: 10.18632/oncotarget.26733
• Hashimoto T, Hashimoto J, Kozone I, Amagai K, Kawahara T, Takahashi S, Ikeda H, Shin-Ya K
  Biosynthesis of Quinolidomicin, the Largest Known Macrolide of Terrestrial Origin: Identification and Heterologous Expression of a Biosynthetic Gene Cluster over 200 kb
  Org Lett. 20: 7996-7999 (2018) doi: 10.1021/acs.orglett.8b03570
• Ohsawa K, Yoshida M, Izumikawa M, Takagi M, Shin-Ya K, Goshima N, Hirokawa T, Natsume T, Doi T
  Synthesis and biological evaluation of thielocin B1 analogues as protein-protein interaction inhibitors of PAC3 homodimer
  Bioorg Med Chem. 10: 185 (2018) doi: 10.1016/j.bmc.2018.11.001
• Thong WL, Shin-Ya K, Nishiyama M, Kuzuyama T
  Discovery of an Antibacterial Isoindolinone-Containing Tetracyclic Polyketide by Cryptic Gene Activation and Characterization of Its Biosynthetic Gene Cluster
  ACS Chem Biol. 13: 2615-2622 (2018) doi: 10.1021/acschembio.8b00553
• Awakawa T, Fujioka T, Zhang L, Hoshino S, Hu Z, Hashimoto J, Kozone I, Ikeda H, Shin-Ya K, Liu W, Abe I
  Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution
  Nat Commun. 9: 3534 (2018) doi: 10.1038/s41467-018-05877-z
• Matsuda K, Tomita T, Shin-Ya K, Wakimoto T, Kuzuyama T, Nishiyama M
  Discovery of Unprecedented Hydrazine-Forming Machinery in Bacteria
  J Am Chem Soc. 140: 9083-9086 (2018) doi: 10.1021/jacs.8b05354
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