生合成システム多様性研究グループ

研究課題

現在上市されている医薬品の6割以上は天然化合物あるいは天然化合物を模倣して合成展開した化合物に由来するように、天然物ライブラリーは創薬スクリーニングのソースとして長く用いられています。我々は、国内有数の製薬系企業提供の天然物ライブラリーを含む、世界最大級の天然物ライブラリーを保有しています。本天然物ライブラリーを用いて、企業およびアカデミア発の創薬ターゲットを対象に、大規模な医薬、動物薬、農薬等のリード化合物探索を展開しています。 　　　　　　　　　　　

従来の発酵法による微生物二次代謝生産では、微生物ゲノム中に存在する生合成遺伝子数の1/3にも満たない能力しか引き出せていないことが明らかになってきています。本研究開発では、難培養微生物由来の未利用生合成遺伝子を含め、種々の微生物の生合成遺伝子を異種ホストに形質転換し、異種発現システムにより、これまで人類が手に入れることの出来なかった新奇天然化合物を創出することを目的としています。また、世界で我々だけが持つ複雑な構造からなる天然化合物の母骨格改変技術を用いて、臨床薬開発に必須な化合物ファインチューニングに貢献します。

天然化合物は医薬品等に応用される生物活性物質の重要なリソースです。極めて複雑な構造を有する天然化合物の誘導体展開は、現代の有機合成でも容易ではなく、新しい手法が求められています。近年我々は、「ポリケタイド」と呼ばれる化合物群の生合成遺伝子を超精密に改変する技術（in vitroモジュール編集技術）の開発に成功しました。ポリケタイド合成酵素遺伝子は非常に類似性が高い配列を繰り返し有するため、従来の遺伝子組換え技術では正確な改変は不可能でしたが、我々の技術を用いることで、自由自在に遺伝子を挿入・置換・欠失させ、新規ポリケタイドを創出することが可能となりました。本技術を基盤として、ポリケタイド骨格の多様性を飛躍的に増大させる技術（コンビナトリアル生合成技術）の開発や、天然化合物と新しい創薬モダリティとの融合、バイオものづくり産業に貢献する新しい有用物質の創出など、基礎及び応用研究を展開しています。

ゲノム機能が的確に発揮されるためには、タンパク質の翻訳後修飾やRNAの転写後修飾が重要であることが近年注目を集めています。RNAが正確に機能するためには、複雑なRNA修飾を受けることが重要である。そこでRNA修飾経路の多様性とその生体内意義を研究します。RNA修飾の異常が疾患の原因となる例が近年多数報告されてきており、オリジナルな基礎研究から新しい創薬シーズの発見を目指します。また生物種による修飾機構の差異を明らかにすることから、副作用のない抗生物質の創出を目指します。

多くの昆虫の体内には様々な共生微生物が存在し、宿主の生理機能に多様な影響を与えています。例えば、昆虫の外骨格を硬くするために必須な共生細菌や、宿主昆虫の生殖様式を変えてしまう共生細菌が存在します。主に、シングルセルゲノム解析やモデル共生系を用いた実験により、その分子メカニズムの解明に取り組んでいます。昆虫は、害虫や益虫など人間社会との関係も深く、またショウジョウバエなどが疾病モデル生物としても用いられることから、昆虫個体群の制御や防除に資する基盤技術の開発や、創薬や治療を支援する技術の開発につながることが期待されます。

多くの昆虫の体内には様々な共生微生物が存在し、宿主の生理機能に多様な影響を与えています。例えば、昆虫の外骨格を硬くするために必須な共生細菌細胞内ではエピジェネティクスなど、単純な遺伝情報を超えた様々なイベントが起きています。我々はエピジェネティックな状態変化をライブイメージングする技術や、細胞内局在情画像報を備えた統合型ヒト完全長cDNAｸﾛｰﾝデータベースなど活用し、遺伝学的情報を超えた細胞の動的な状態を研究し、生物の理解や創薬に繋げる研究を推進します。具体的には、哺乳類でみられるエピジェネティックな制御で知られる「X染色体不活性化」や、核内の様々な反応の制御・調節に働く「非膜構造体」などを対象とした研究を行っています。

業績リスト

• Hashimoto, T; Suenaga, H; Shin-Ya, K.
  Application of Cas9-Based Gene Editing to Engineering of Nonribosomal Peptide Synthetases.
  CHEMBIOCHEM. 2024 Dec 30:e202400765. doi:10.1002/cbic.202400765
• Kudo, K; Nishimura, T; Miyako, K; Suenaga, H; Shin-Ya, K.
  A new cannabigerolic acid derivative and its unprenylated precursor produced through the reconstitution of cannabinoid biosynthesis in Streptomyces.
  J ANTIBIOT (Tokyo). 2024 Dec 3. doi:10.1038/s41429-024-00793-5
• Yamamoto, K; Uzaki, M;Takahashi, K; Mimura, T.
  Current status of MSI research in Japan to measure the localization of natural products in plants.
  CURR OPIN PLANT BIOL. 2024 Oct 19;82:102651. doi: 10.1016/j.pbi.2024.102651
• 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
• Bharti SK, Sommers JA, Awate S, Bellani MA, Khan I, Bradley L, King GA, Seol Y, Vidhyasagar V, Wu Y, Abe T, Kobayashi K, Shin-Ya K, Kitao H, Wold MS, Branzei D, Neuman KC, Brosh RM Jr
  A minimal threshold of FANCJ helicase activity is required for its response to replication stress or double-strand break repair
  Nucleic Acids Res. 46: 6238-6256 (2018) doi: 10.1093/nar/gky403
• Kim JH, Komatsu M, Shin-Ya K, Omura S, Ikeda H
  Distribution and functional analysis of the phosphopantetheinyl transferase superfamily in Actinomycetales microorganisms
  Proc Natl Acad Sci U S A. 115: 6828-6833 (2018) doi: 10.1073/pnas.1800715115
• Tsutsumi H, Katsuyama Y, Izumikawa M, Takagi M, Fujie M, Satoh N, Shin-ya K, Ohnishi Y
  Unprecedented Cyclization Catalyzed by a Cytochrome P450 in Benzastatin Biosynthesis
  J Am Chem Soc. 140: 6631-6639 (2018) doi: 10.1021/jacs.8b02769
• Kimura N, Watanabe T, Suenaga H, Fujihara H, Futagami T, Goto M, Hanada S, Hirose J
  Pseudomonas furukawaii sp nov., a polychlorinated biphenyl-degrading bacterium isolated from biphenyl-contaminated soil in Japan
  Int J Sys Evol Microbiol. 68: 1429-1435 (2018) doi: 10.1099/ijsem.0.002670
• Shigi N
  Recent Advances in Our Understanding of the Biosynthesis of Sulfur Modifications in tRNAs
  Front Microbiol. 67: 347-353 (2018) doi: 10.3389/fmicb.2018.02679
• Kawahara T, Fujiwara T, Kagaya N, Shin-Ya K
  JBIR-150, a novel 20-membered polyene macrolactam from marine-derived Streptomyces sp. OPMA00071
  J Antibiot. 71: 390-392 (2018) doi: 10.1038/s41429-017-0010-2
• Kawahara T, Izumikawa M, Kozone I, Hashimoto J, Kagaya N, Koiwai H, Komatsu M, Fujie M, Sato N, Ikeda H, Shin-Ya K
  Neothioviridamide, a Polythioamide Compound Produced by Heterologous Expression of a Streptomyces sp. Cryptic RiPP Biosynthetic Gene Cluster
  J Nat Prod. 81: 264-269 (2018) doi: 10.1021/acs.jnatprod.7b00607
• Du D, Katsuyama Y, Shin-Ya K, Ohnishi Y
  Reconstitution of a Type II Polyketide Synthase that Catalyzes Polyene Formation
  Angew Chem Int Ed Engl. 57: 1954-1957 (2018) doi: 10.1002/anie.201709636
• Niikura H, Maruyama C, Ogasawara Y, Shin-ya K, Dairi T, Hamano Y
  Functional analysis of methyltransferases participating in streptothricin-related antibiotic biosynthesis
  J Biosci Bioeng. 125: 148-154 (2018) doi: 10.1016/j.jbiosc.2017.09.004
• Ito S, Ogawa K, Takeuchi K, Takagi M, Yoshida M, Hirokawa T, Hirayama S, Shin-ya K, Shimada I, Doi T, Goshima N, Natsume T, Nagata K
  A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis
  J Biol Chem. 292: 20076-20085 (2017) doi: 10.1074/jbc.M117.815936
• Suenaga H, Fujihara H, Kimura N, Hirose J, Watanabe T, Futagami T, Goto M, Shimodaira J, Furukawa K
  Insights into the genomic plasticity of Pseudomonas putida KF715, a strain with unique biphenyl-utilizing activity and genome instability properties
  Environ Microbiol Rep. 9: 589-598 (2017) doi: 10.1111/1758-2229.12561
• Takeda K, Kemmoku K, Satoh Y, Ogasawara Y, Shin-ya K, Dairi T
  N-Phenylacetylation and Nonribosomal Peptide Synthetases with Substrate Promiscuity for Biosynthesis of Heptapeptide Variants, JBIR-78 and JBIR-95
  ACS Chem Biol. 12: 1813-1819 (2017) doi: 10.1021/acschembio.7b00314
• 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
• Nakamura T, Okabe S, Yoshida H, Iida K, Ma Y, Sasaki S, Yamori T, Shin-Ya K, Nakano I, Nagasawa K, Seimiya H
  Targeting glioma stem cells in vivo by a G-quadruplex-stabilizing synthetic macrocyclic hexaoxazole
  Sci Rep. 7: 3605 (2017) doi: 10.1038/s41598-017-03785-8
• Chen M, Asai SI, Narai S, Nambu S, Omura N, Sakaguchi Y, Suzuki T, Ikeda-Saito M, Watanabe K, Yao M, Shigi N, Tanaka Y
  Biochemical and structural characterization of oxygen-sensitive 2-thiouridine synthesis catalyzed by an iron-sulfur protein TtuA
  Proc Natl Acad Sci U S A. 114: 4954-4959 (2017) doi: 10.1073/pnas.1615585114
• Kudo K, Ozaki T, Shin-ya K, Nishiyama M, Kuzuyama T
  Biosynthetic Origin of the Hydroxamic Acid Moiety of Trichostatin A: Identification of Unprecedented Enzymatic Machinery Involved in Hydroxylamine Transfer
  J Am Chem Soc. 139: 6799-6802 (2017) doi: 10.1021/jacs.7b0207110.1093/dnares/dsw055
• Takami H, Toyoda A, Uchiyama I, Itoh T, Takaki Y, Arai W, Nishi, S, Kawai M, Shin-ya K, Ikeda H
  Complete genome sequence and expression profile of the commercial lytic enzyme producer Lysobacter enzymogenes M497-1
  DNA Res. 24: 169-177 (2017) doi: 10.1093/dnares/dsw055