Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Pharmaceutical Sciences　Molecular Pharmaceutical Sciences　Chemistry and Medicinal Chemistry

Affiliation (Master)

• Faculty of Pharmaceutical Sciences　Molecular Pharmaceutical Sciences　Chemistry and Medicinal Chemistry

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Profile and Settings

Profile and Settings

• Name (Japanese)

  Matsuda

• Name (Kana)

  Kenichi

• Name

  201701020517747574

Alternate Names

https://www.pharm.hokudai.ac.jp/tennen/

Achievement

Research Interests

• Actinomycetes   Genome mining   Biosynthesis   Natural product chemistry   

Research Areas

• Life sciences / Bioorganic chemistry / natural product chemistry

Research Experience

• 2024/09 - Today Hokkaido University Faculty of Pharmaceutical Sciences
• 2021/09 - 2024/08 Hokkaido University Faculty of Pharmaceutical Sciences
• 2017/09 - 2021/08 Hokkaido University Faculty of Pharmaceutical Sciences
• 2017/06 - 2017/08 Hokkaido University Faculty of Pharmaceutical Sciences
• 2017/04 - 2017/05 次世代天然物化学技術研究組合 博士研究員

Awards

• 2024/10 日本放線菌学会 浜田賞 (研究奨励賞)
   放線菌由来天然物生合成酵素を用いた環状ペプチドの化学-酵素合成
• 2023/09 生体触媒化学シンポジウム 第23回 生体触媒化学シンポジウム The company spotlight presentation award
   

  受賞者: 松田研一
• 2022/09 日本生薬学会 学術奨励賞
   天然物生合成におけるペプチド修飾反応に関する研究 

  受賞者: 松田研一
• 2021/10 第58回ペプチド討論会 第58回ペプチド討論会 若手優秀発表賞
   Enzymatic basis of guanidine bis-prenylation in argicyclamide biosynthesis 

  受賞者: Kenichi Matsuda;Chin-Soon Phan;Nandani Balloo;Kei Fujita;Tatsufumi Okino;Toshiyuki Wakimoto
• 2021/10 第63回天然有機化合物討論会 第63回天然有機化合物討論会 奨励賞 口頭発表の部
   窒素－窒素結合含有天然物のゲノムマイニング 

  受賞者: 松田研一;有馬陸;秋山智子;阿部葉;城内航;新家一男;脇本敏幸
• 2021/10 日本薬学会生薬天然物部会 令和3年度 日本薬学会生薬天然物部会 奨励研究
   

  受賞者: 松田研一

Published Papers

• Doubly Homologated Tyrosine-Containing Peptides from the Cyanobacterium Microcystis aeruginosa NIES-4285 and Their Biosynthesis

  Chin-Soon Phan, Zhengyi Ling, Jakia Jerin Mehjabin, Kenichi Matsuda, Nurcahyo Iman Prakoso, Taiki Umezawa, Toshiyuki Wakimoto, Tatsufumi Okino

  Journal of Natural Products 0163-3864 2024/10/30
• Synthesis and Cytotoxicity of Cyclic Octapeptide Surugamides with Varied N-Acyl Moieties

  Kenichi Matsuda, Shinya Niikura, Rintaro Ichihara, Kei Fujita, Anna M. Strasser, Rokusuke Yoshikawa, Jiro Yasuda, Yoshiki Hiramatsu, Hironori Hayashi, Eiichi N. Kodama, Toshiyuki Wakimoto

  Chemical and Pharmaceutical Bulletin 72 (9) 826 - 830 0009-2363 2024/09/20 [Refereed]
  
• Macrocyclizing-thioesterases in bacterial non-ribosomal peptide biosynthesis.

  Kenichi Matsuda

  Journal of natural medicines 2024/08/30 [Refereed][Invited]
   

  Macrocyclization of peptides reduces conformational flexibilities, potentially leading to improved drug-like properties. However, side reactions such as epimerization and oligomerization often pose synthetic challenges. Peptide-cyclizing biocatalysts in the biosynthesis of non-ribosomal peptides (NRPs) have remarkable potentials as chemoenzymatic tools to facilitate more straightforward access to complex macrocycles. This review highlights the biocatalytic potentials of NRP cyclases, especially those of cis-acting thioesterases, the most general cyclizing machinery in NRP biosynthesis. Growing insights into penicillin-binding protein-type thioesterases, a relatively new group of trans-acting thioesterases, are also summarized.
• FlkO, a penicillin-binding protein-type thioesterase in cyclofaulknamycin biosynthesis

  Kenichi Matsuda, Rintaro Ichihara, Toshiyuki Wakimoto

  Organic & Biomolecular Chemistry 1477-0520 2024/08 [Refereed][Not invited]
   

  In vitro studies of FlkO, a new penicillin-binding protein thioesterase, demonstrated its peptide-cyclizing activity and substrate scope.
• Penicillin-binding protein-type thioesterases: An emerging family of non-ribosomal peptide cyclases with biocatalytic potentials

  Kenichi Matsuda, Toshiyuki Wakimoto

  Current Opinion in Chemical Biology 2024/06 [Refereed][Not invited]
  
• Chemoenzymatic tandem cyclization for the facile synthesis of bicyclic peptides

  Masakazu Kobayashi, Naho Onozawa, Kenichi Matsuda, Toshiyuki Wakimoto

  Communications Chemistry 7 (1) 2024/03/28 [Refereed][Not invited]
   

  Abstract Bicyclic peptides exhibit improved metabolic stabilities and target specificities when compared to their linear or mono-cyclic counterparts; however, efficient and straightforward synthesis remains challenging due to their intricate architectures. Here, we present a highly selective and operationally simple one-pot chemoenzymatic tandem cyclization approach to synthesize bicyclic peptides with small to medium ring sizes. Penicillin-binding protein-type thioesterases (PBP-type TEs) efficiently cyclized azide/alkyne-containing peptides in a head-to-tail manner. Successive copper (I)-catalyzed azide-alkyne cycloaddition generated bicyclic peptides in one-pot, thus omitting the purification of monocyclic intermediates. This chemoenzymatic strategy enabled the facile synthesis of bicyclic peptides bearing hexa-, octa-, and undecapeptidyl head-to-tail cyclic scaffolds.
• Bacterial hydrazine biosynthetic pathways featuring cupin/methionyl tRNA synthetase-like enzymes.

  Kenichi Matsuda, Toshiyuki Wakimoto

  Chembiochem : a European journal of chemical biology e202300874  2024/03/08 [Refereed][Not invited]
   

  Nitrogen-Nitrogen (N-N) bond-containing functional groups in natural products and synthetic drugs play significant roles in exerting biological activities. The mechanisms of N-N bond formation in natural organic molecules have garnered increasing attention over the decades. Recent advances have illuminated various enzymatic and nonenzymatic strategies, and our understanding of natural N-N bond construction is rapidly expanding. A group of didomain proteins with zinc-binding cupin/methionyl-tRNA synthetase (MetRS)-like domains, also known as hydrazine synthetases, generates amino acid-based hydrazines, which serve as key biosynthetic precursors of diverse N-N bond-containing functionalities such as hydrazone, diazo, triazene, pyrazole, and pyridazinone groups. In this review, we summarize the current knowledge on hydrazine synthetase mechanisms and the various pathways employing this unique bond-forming machinery.
• Phylogeny‐guided Characterization of Bacterial Hydrazine Biosynthesis Mediated by Cupin/methionyl tRNA Synthetase‐like Enzymes

  Kenichi Matsuda, Yuto Nakahara, Atina Rizkiya Choirunnisa, Kuga Arima, Toshiyuki Wakimoto

  ChemBioChem 1439-4227 2024/02/25 [Refereed]
   

  Cupin/methionyl‐tRNA synthetase (MetRS)‐like didomain enzymes catalyze nitrogen‐nitrogen (N–N) bond formation between Nw‐hydroxylamines and amino acids to generate hydrazines, key biosynthetic intermediates of various natural products containing N–N bonds. While the combination of these two building blocks leads to the creation of diverse hydrazine products, the full extent of their structural diversity remains largely unknown. To explore this, we herein conducted phylogeny‐guided genome‐mining of related hydrazine biosynthetic pathways consisting of two enzymes: flavin‐dependent Nw‐hydroxylating monooxygenases (NMOs) that produce Nw‐hydroxylamine precursors and cupin/MetRS‐like enzymes that couple the Nw‐hydroxylamines with amino acids via N–N bonds. A phylogenetic analysis identified the largely unexplored sequence spaces of these enzyme families. The biochemical characterization of NMOs demonstrated their capabilities to produce various Nw‐hydroxylamines, including those previously not known as precursors of N–N bonds. Furthermore, the characterization of cupin/MetRS‐like enzymes identified five new hydrazine products with novel combinations of building blocks, including one containing non‐amino acid building blocks: 1,3‐diaminopropane and putrescine. This study substantially expanded the variety of N–N bond forming pathways mediated by cupin/MetRS‐like enzymes.
• Actinobacterial chalkophores: the biosynthesis of hazimycins

  Kenichi Matsuda, Hiroto Maruyama, Kumiko Imachi, Haruo Ikeda, Toshiyuki Wakimoto

  The Journal of Antibiotics 2024/02/20 [Refereed][Not invited]
  
• Carrier Protein Mediated Formation of the Dihydropyridazinone Ring in Actinopyridazinone Biosynthesis

  Kuga Arima, Satoko Akiyama, Kazuo Shin-ya, Kenichi Matsuda, Toshiyuki Wakimoto

  Angewandte Chemie International Edition 1433-7851 2023/05/17 [Refereed]
  
• Characterization of the surugamide biosynthetic gene cluster of TUA-NKU25, a Streptomyces diastaticus strain isolated from Kusaya, and its effects on salt-dependent growth

  Aoi Takeuchi, Asahi Hirata, Aiko Teshima, Miu Ueki, Takumi Satoh, Kenichi Matsuda, Toshiyuki Wakimoto, Kenji Arakawa, Morio Ishikawa, Toshihiro Suzuki

  Bioscience, Biotechnology, and Biochemistry 2023/02/24 [Refereed][Not invited]
   

  Abstract Kusaya, a traditional Japanese fermented fish product, is known for its high preservability, as it contains natural antibiotics derived from microorganisms, and therefore molds and yeasts do not colonize it easily. In this study, the Streptomyces diastaticus strain TUA-NKU25 was isolated from Kusaya; its growth as well as the production of antibiotics were investigated. Strain TUA-NKU25 showed advantageous growth characteristics in the presence, but not in the absence of NaCl. Antimicrobial assay, high-performance liquid chromatography, and electrospray ionization-mass spectrometry analysis showed that this strain produced surugamide A and uncharacterized antimicrobial compound(s) during growth in the presence of NaCl, suggesting that biosynthesis of these compounds was upregulated by NaCl. Draft genomic analysis revealed that strain TUA-NKU25 possesses a surugamide biosynthetic gene cluster (sur BGC), although it is incomplete, lacking surB/surC. Phylogenetic analysis of strain TUA-NKU25 and surugamide-producing Streptomyces showed that sur BGC formed a clade distinct from other known groups.
• Streamlined Chemoenzymatic Synthesis of Cyclic Peptides by Non-ribosomal Peptide Cyclases

  Masakazu Kobayashi, Kei Fujita, Kenichi Matsuda, Toshiyuki Wakimoto

  Journal of the American Chemical Society 145 (6) 3270 - 3275 0002-7863 2023/01/13 [Refereed][Not invited]
  
• Chemo-Enzymatic Synthesis of Non-ribosomal Macrolactams by a Penicillin-Binding Protein-Type Thioesterase.

  Masakazu Kobayashi, Kei Fujita, Kenichi Matsuda, Toshiyuki Wakimoto

  Methods in molecular biology (Clifton, N.J.) 2670 127 - 144 2023 [Refereed][Invited]
   

  Penicillin-binding protein-type thioesterases (PBP-type TEs) are an emerging family of non-ribosomal peptide cyclases. PBP-type TEs exhibit distinct substrate scopes from the well-exploited ribosomal peptide cyclases and traditional non-ribosomal peptide cyclases. Their unique properties, as well as their stand-alone nature, highlight PBP-type TEs as valuable candidates for development as biocatalysts for peptide macrocyclization. Here in this chapter, we describe the scheme for the chemoenzymatic synthesis of non-ribosomal macrolactam by SurE, a representative member of PBP-type TEs.
• Molecular Basis for Enzymatic Aziridine Formation via Sulfate Elimination

  Sumire Kurosawa, Fumihito Hasebe, Hironori Okamura, Ayako Yoshida, Kenichi Matsuda, Yusuke Sone, Takeo Tomita, Tetsuro Shinada, Hirosato Takikawa, Tomohisa Kuzuyama, Saori Kosono, Makoto Nishiyama

  Journal of the American Chemical Society 144 (35) 16164 - 16170 0002-7863 2022/08/23 [Refereed]
   

  Natural products containing an aziridine ring, such as mitomycin C and azinomycin B, exhibit antitumor activities by alkylating DNA via their aziridine rings; however, the biosynthetic mechanisms underlying the formation of these rings have not yet been elucidated. We herein investigated the biosynthesis of vazabitide A, the structure of which is similar to that of azinomycin B, and demonstrated that Vzb10/11, with no similarities to known enzymes, catalyzed the formation of the aziridine ring via sulfate elimination. To elucidate the detailed reaction mechanism, crystallization of Vzb10/11 and the homologous enzyme, AziU3/U2, in the biosynthesis of azinomycin B was attempted, and the structure of AziU3/U2, which had a new protein fold overall, was successfully determined. The structural analysis revealed that these enzymes adjusted the dihedral angle between the amino group and the adjacent sulfate group of the substrate to almost 180° and enhanced the nucleophilicity of the C6-amino group temporarily, facilitating the SN2-like reaction to form the aziridine ring. The present study reports for the first time the molecular basis for aziridine ring formation.
• New azodyrecins identified by a genome mining-directed reactivity-based screening

  Atina Rizkiya Choirunnisa, Kuga Arima, Yo Abe, Noritaka Kagaya, Kei Kudo, Hikaru Suenaga, Junko Hashimoto, Manabu Fujie, Noriyuki Satoh, Kazuo Shin-ya, Kenichi Matsuda, Toshiyuki Wakimoto

  Beilstein Journal of Organic Chemistry 18 1017 - 1025 1860-5397 2022/08/10 [Refereed][Not invited]
   

  Only a few azoxy natural products have been identified despite their intriguing biological activities. Azodyrecins D–G, four new analogs of aliphatic azoxides, were identified from two Streptomyces species by a reactivity-based screening that targets azoxy bonds. A biological activity evaluation demonstrated that the double bond in the alkyl side chain is important for the cytotoxicity of azodyrecins. An in vitro assay elucidated the tailoring step of azodyrecin biosynthesis, which is mediated by the S-adenosylmethionine (SAM)-dependent methyltransferase Ady1. This study paves the way for the targeted isolation of aliphatic azoxy natural products through a genome-mining approach and further investigations of their biosynthetic mechanisms.
• A Natural Dihydropyridazinone Scaffold Generated from a Unique Substrate for a Hydrazine-Forming Enzyme

  Kenichi Matsuda, Kuga Arima, Satoko Akiyama, Yuito Yamada, Yo Abe, Hikaru Suenaga, Junko Hashimoto, Kazuo Shin-ya, Makoto Nishiyama, Toshiyuki Wakimoto

  Journal of the American Chemical Society 144 (28) 12954 - 12960 0002-7863 2022/06/30 [Refereed]
   

  Nitrogen-nitrogen bond-containing functional groups are rare, but they are found in a considerably wide class of natural products. Recent clarifications of the biosynthetic routes for such functional groups shed light onto overlooked biosynthetic genes distributed across the bacterial kingdom, highlighting the presence of yet-to-be identified natural products with peculiar functional groups. Here, the genome-mining approach targeting a unique hydrazine-forming gene led to the discovery of actinopyridazinones A (1) and B (2), the first natural products with dihydropyridazinone rings. The structure of actinopyridazinone A was unambiguously established by total synthesis. Biosynthetic studies unveiled the structural diversity of natural hydrazines derived from this family of N-N bond-forming enzymes.
• Insights into Phosphatase-activated Chemical Defense in a Marine Sponge Holobiont

  Jomori, T, Matsuda, K, Egami, Y, Abe, I, Takai, A, Wakimoto, T

  RSC Chemical Biology 2021/10 [Refereed]
   

  Marine sponges often contain potent cytotoxic compounds, which in turn evokes the principle question of how marine sponges avoid self-toxicity. In a marine sponge Discodermia calyx, the highly toxic calyculin...
• Argicyclamides A-C Unveil Enzymatic Basis for Guanidine Bis-prenylation.

  Chin-Soon Phan, Kenichi Matsuda, Nandani Balloo, Kei Fujita, Toshiyuki Wakimoto, Tatsufumi Okino

  Journal of the American Chemical Society 2021/06/28 [Refereed]
   

  Guanidine prenylation is an outstanding modification in alkaloid and peptide biosynthesis, but its enzymatic basis has remained elusive. We report the isolation of argicyclamides, a new class of cyanobactins with unique mono- and bis-prenylations on guanidine moieties, from Microcystis aeruginosa NIES-88. The genetic basis of argicyclamide biosynthesis was established by the heterologous expression and in vitro characterization of biosynthetic enzymes including AgcF, a new guanidine prenyltransferase. This study provides important insight into the biosynthesis of prenylated guanidines and offers a new toolkit for peptide modification.
• PenA, a penicillin-binding protein-type thioesterase specialized for small peptide cyclization.

  Kenichi Matsuda, Kei Fujita, Toshiyuki Wakimoto

  Journal of industrial microbiology & biotechnology 48 (3-4) 2021/03/13 [Refereed]
   

  Penicillin binding protein-type thioesterases (PBP-type TEs) are a recently identified group of peptide cyclases that catalyze head-to-tail macrolactamization of non-ribosomal peptides. PenA, a new member of this group, is involved in the biosyntheses of cyclic pentapeptides. In this study, we demonstrated the enzymatic activity of PenA in vitro, and analyzed its substrate scope with a series of synthetic substrates. A comparison of the reaction profiles between PenA and SurE, a representative PBP-type TE, showed that PenA is more specialized for small peptide cyclization. A computational model provided a possible structural rationale for the altered specificity for substrate chain lengths.
• Recent advance in the biosynthesis of nitrogen–nitrogen bond–containing natural products

  Yohei Katsuyama, Kenichi Matsuda

  Current Opinion in Chemical Biology 59 62 - 68 2020/12 [Refereed][Invited]
  
• Total Synthesis and Structural Revision of Kasumigamide, and Identification of a New Analogue

  Takefumi Kuranaga, Kenichi Matsuda, Masachika Takaoka, Chisato Tachikawa, Ayae Sano, Kosei Itoh, Ayumu Enomoto, Kei Fujita, Ikuro Abe, Toshiyuki Wakimoto

  ChemBioChem 1439-4227 2020/07/21 [Refereed][Not invited]
   

  © 2020 Wiley-VCH GmbH Kasumigamide is an antialgal hybrid peptide–polyketide isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES-87). The biosynthetic gene cluster was identified from not only the cyanobacterium but also Candidatus “Entotheonella”, associated with the Japanese marine sponge Discodermia calyx. Therefore, kasumigamide is considered to play a key role in microbial ecology, regardless of the terrestrial and marine habitats. We now report synthetic studies on this intriguing natural product that have led to a structural revision and the first total synthesis. During this study, a new analogue, deoxykasumigamide, was also isolated and structurally validated. This study confirmed the presence of the unusual pathway in the biosynthesis of a hybrid peptide–polyketide natural product.
• Guanidyl modification of the 1-azabicyclo[3.1.0]hexane ring in ficellomycin essential for its biological activity.

  Sumire Kurosawa, Kenichi Matsuda, Fumihito Hasebe, Taro Shiraishi, Kazuo Shin-Ya, Tomohisa Kuzuyama, Makoto Nishiyama

  Organic & biomolecular chemistry 18 (27) 5137 - 5144 2020/07/15 [Refereed][Not invited]
   

  The 1-azabicyclo[3.1.0]hexane ring is a key moiety in natural products for biological activities against bacteria, fungi, and tumor through DNA alkylation. Ficellomycin is a dipeptide that consists of l-valine and a non-proteinogenic amino acid with the 1-azabicyclo[3.1.0]hexane ring structure. Although the biosynthetic gene cluster of ficellomycin has been identified, the biosynthetic pathway currently remains unclear. We herein report the final stage of ficellomycin biosynthesis involving ring modifications and successive dipeptide formation. After the ring is formed, the hydroxy group of the ring is converted into the guanidyl unit by three enzymes, which include an aminotransferase with a novel inter ω-ω amino-transferring activity. In the last step, the resulting 1-azabicyclo[3.1.0]hexane ring-containing amino acid is connected with l-valine by an amino acid ligase to yield ficellomycin. The present study revealed a new machinery that expands the structural and biological diversities of natural products.
• Heterochiral coupling in non-ribosomal peptide macrolactamization

  Kenichi Matsuda, Rui Zhai, Takahiro Mori, Masakazu Kobayashi, Ayae Sano, Ikuro Abe, Toshiyuki Wakimoto

  Nature Catalysis 3 (6) 507 - 515 2020/05/04
• A suicide enzyme catalyzes multiple reactions for biotin biosynthesis in cyanobacteria.

  Kei Sakaki, Keita Ohishi, Tetsu Shimizu, Ikki Kobayashi, Naoki Mori, Kenichi Matsuda, Takeo Tomita, Hidenori Watanabe, Kan Tanaka, Tomohisa Kuzuyama, Makoto Nishiyama

  Nature chemical biology 16 (4) 415 - 422 2020/02/10 [Refereed][Not invited]
   

  In biotin biosynthesis, the conversion of pimeloyl intermediates to biotin is catalyzed by a universal set of four enzymes: BioF, BioA, BioD and BioB. We found that the gene homologous to bioA, the product of which is involved in the conversion of 8-amino-7-oxononanoate (AON) to 7,8-diaminononanoate (DAN), is missing in the genome of the cyanobacterium Synechocystis sp. PCC 6803. We provide structural and biochemical evidence showing that a novel dehydrogenase, BioU, is involved in biotin biosynthesis and functionally replaces BioA. This enzyme catalyzes three reactions: formation of covalent linkage with AON to yield a BioU-DAN conjugate at the ε-amino group of Lys124 of BioU using NAD(P)H, carboxylation of the conjugate to form BioU-DAN-carbamic acid, and release of DAN-carbamic acid using NAD(P)+. In this biosynthetic pathway, BioU is a suicide enzyme that loses the Lys124 amino group after a single round of reaction.
• A New Cyclase Family Catalyzing Head-to-Tail Macrolactamization of Non-ribosomal Peptides

  Kenichi Matsuda

  Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 77 (11) 1106 - 1115 2019/11 [Refereed][Invited]
  
• Scrobiculosides A and B from the deep-sea sponge Pachastrella scrobiculosa.

  Jomori T, Shiroyama S, Ise Y, Kohtsuka H, Matsuda K, Kuranaga T, Wakimoto T

  Journal of natural medicines 73 (4) 814 - 819 1340-3443 2019/05 [Refereed][Not invited]
   

  Two new steroidal saponins, scrobiculosides A and B, were isolated from the deep-sea sponge Pachastrella scrobiculosa, collected at a depth of 200 m off Miura Peninsula, Japan. The aglycones of scrobiculosides A and B feature a vinylic cyclopropane and a ∆24,25 exomethylene on the side chains, respectively. Both saponins have a common sugar moiety composed of β-D-galactopyranosyl-(1 → 2)-6-acetyl-β-D-glucopyranoside, with the exception of an acetyl group on C6″ in scrobiculoside A. Scrobiculoside A exhibited cytotoxicity against HL-60 and P388 cells, with IC50 values of 52 and 61 μM, respectively.
• Immunosuppressive effect of a non-proteinogenic amino acid from Streptomyces through inhibiting allogeneic T cell proliferation.

  Yashiro T, Sakata F, Sekimoto T, Shirai T, Hasebe F, Matsuda K, Kurosawa S, Suzuki S, Nagata K, Kasakura K, Nishiyama M, Nishiyama C

  Bioscience, biotechnology, and biochemistry 83 (6) 1 - 6 0916-8451 2019/03 [Refereed][Not invited]
   

  The immunosuppressive activity of myriocin (ISP-1), a lead compound of fingolimod (FTY720), is derived from its 2-amino-1,3-propandiol structure. A non-proteinogenic amino acid, (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), that contains this structure, was recently identified as a biosynthetic intermediate of a dipeptide secondary metabolite, vazabitide A, in Streptmyces sp. SANK 60404; however its effect on adaptive immunity has not yet been examined. In this study, we examined whether DADH suppresses mixed lymphocyte reaction using mouse bone marrow-derived dendritic cells (BMDCs) and allogeneic splenic T cells. Although T cell proliferation induced by cross-linking CD3 and CD28 were not suppressed by DADH unlike ISP-1, the pre-incubation of BMDCs with DADH but not ISP-1 significantly decreased allogeneic CD8+ T cell expansion. Based on these results, we concluded that DADH suppresses DC-mediated T cell activation by targeting DCs.
• The revised structure of the cyclic octapeptide surugamide A

  K. Matsuda, T. Kuranaga, A. Sano, A. Ninomiya, K. Takada, T. Wakimoto

  Chem. Pharm. Bull in press (5) 476 - 480 0009-2363 2019 [Refereed][Not invited]
   

  Surugamides are a group of non-ribosomal peptides isolated from marine-derived Streptomyces. Surugamide A (1) and its closely related derivatives, surugamides B-E (2-5), are D-amino acid containing cyclic octapeptides with cathepsin B inhibitory activity. The D-isoleucine (Ile), the nonproteinogenic amino acid residue embedded in 1, is less common in natural peptides because a rare Cβ-epimerization is required for its biosynthesis. Taking advantage of the synthetic route of 2 previously established by our group, we synthesized the cyclic octapeptide 1 containing D-Ile by solid phase peptide synthesis. The structure of 1 actually contains D-allo-Ile in place of D-Ile, which was corroborated by chemical syntheses and chromatographic comparisons.
• SurE is a trans-acting thioesterase cyclizing two distinct non-ribosomal peptides.

  Matsuda K, Kobayashi M, Kuranaga T, Takada K, Ikeda H, Matsunaga S, Wakimoto T

  Organic & biomolecular chemistry 1477-0520 2019/01 [Refereed][Not invited]
  
• Discovery of Unprecedented Hydrazine-Forming Machinery in Bacteria.

  Matsuda K, Tomita T, Shin-Ya K, Wakimoto T, Kuzuyama T, Nishiyama M

  Journal of the American Chemical Society 140 (29) 9083 - 9086 0002-7863 2018/07 [Refereed][Not invited]
   

  Recent studies described several different routes that facilitate nitrogen-nitrogen bond formation in natural product biosynthesis. We report herein the identification of unprecedented machinery for hydrazine formation involved in the biosynthesis of s56-p1, a dipeptide natural product with a unique hydrazone unit. The gene cassette comprising this machinery is widespread across several bacterial phyla, highlighting the overlooked potential of bacteria to synthesize hydrazine.
• Total Synthesis of the Nonribosomal Peptide Surugamide B and Identification of a New Offloading Cyclase Family.

  Kuranaga T, Matsuda K, Sano A, Kobayashi M, Ninomiya A, Takada K, Matsunaga S, Wakimoto T

  Angewandte Chemie (International ed. in English) 57 (30) 9447 - 9451 1433-7851 2018/05 [Refereed][Not invited]
   

  The cathepsin B inhibitor surugamide B (2), along with structurally related derivatives (A and C-E), has previously been isolated from the marine actinomycete Streptomyces sp. JAMM992. The biosynthetic genes are unexpectedly part of a cluster of four non-ribosomal peptide synthetase (NRPS) genes, two of which are responsible for the biosynthesis of the additional linear decapeptide surugamide F. However, the thioesterase domain required for the later stage of the biosynthesis of the cyclic peptides surugamides A-E is not present in any module architecture of the surugamide NRPSs. Herein, we report the first total synthesis of surugamide B (2) through the macrocyclization at the biomimetic position, which not only alleviated the Cα epimerization in the macrolactamization process, but also efficiently provided 2 in 34 % yield for 18 steps. Furthermore, both the chemical and enzymatic studies with the biosynthetic precursor mimics revealed that the stand-alone enzyme SurE, which belongs to the penicillin-binding protein family, is responsible for macrocyclization of the tethered octapeptidyl intermediate.
• Genome Mining of Amino Group Carrier Protein-Mediated Machinery: Discovery and Biosynthetic Characterization of a Natural Product with Unique Hydrazone Unit

  Kenichi Matsuda, Fumihito Hasebe, Yuh Shiwa, Yu Kanesaki, Takeo Tomita, Hirofumi Yoshikawa, Kazuo Shin-ya, Tomohisa Kuzuyama, Makoto Nishiyama

  ACS CHEMICAL BIOLOGY 12 (1) 124 - 131 1554-8929 2017/01 [Refereed][Not invited]
   

  We recently revealed that a Streptomyces strain possesses the gene encoding amino group carrier protein (AmCP). AmCP is involved in the biosynthesis of a previously unidentified non-proteinogenic amino acid, (25,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), which is a core compound for the synthesis of the dipeptide-containing novel natural product vazabitide A. We used polymerase chain reaction (PCR) screening to investigate the diversity of the biosynthetic machinery that uses AmCP; the results revealed that genes encoding AmCP are widely distributed among actinomycetes. The heterologous expression of the AmCP-containing gene cluster from Streptomyces sp. SoC090715LN-17 led to the discovery of s56-p1, a novel natural product. The structure of s56-p1 was determined by spectroscopic analysis; the results revealed that s56-p1 has a putative DADH-derived molecule as the core and also possesses a unique hydrazone unit that is rarely observed in natural products. Our results pave the way for investigations of unexploited AmCP-mediated biosynthesis routes among actinomycetes and of the biosynthetic mechanism of the unique hydrazone unit.
• Amino-group carrier-protein-mediated secondary metabolite biosynthesis in Streptomyces

  Fumihito Hasebe, Kenichi Matsuda, Taro Shiraishi, Yushi Futamura, Takeshi Nakano, Takeo Tomita, Ken Ishigami, Hikari Taka, Reiko Mineki, Tsutomu Fujimura, Hiroyuki Osada, Tomohisa Kuzuyama, Makoto Nishiyama

  NATURE CHEMICAL BIOLOGY 12 (11) 967 - + 1552-4450 2016/11 [Refereed][Not invited]
   

  Amino-group carrier proteins (AmCPs) mediate the biosynthesis of lysine and arginine in some bacteria and archaea. Here we demonstrate that an uncharacterized AmCP-mediated biosynthetic system functions to biosynthesize the previously uncharacterized and nonproteinogenic amino acid (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH) in Streptomyces sp. SANK 60404. DADH is incorporated into a novel peptide metabolite, vazabitide A, featuring an azabicyclo-ring structure, by nonribosomal peptide synthetases and successive modification enzymes in this bacterium. As the AmCP-mediated machinery for DADH biosynthesis is widely distributed in bacteria, further analysis of uncharacterized AmCP-containing gene clusters will lead to the discovery of novel bioactive compounds and novel biosynthetic enzymes.
• Crystallization and preliminary X-ray diffraction analysis of cyclolavandulyl diphosphate synthase, a new member of the cis-isoprenyl diphosphate synthase superfamily

  Takeo Tomita, Taro Ozaki, Kenichi Matsuda, Makoto Nishiyama, Tomohisa Kuzuyama

  Acta Crystallographica Section F:Structural Biology Communications 70 1410 - 1413 2053-230X 2014/10/01 [Refereed][Not invited]
   

  Cyclolavandulyl diphosphate synthase (CLDS estimated molecular weight 23.1 kDa) from the soil bacterium Streptomyces sp. CL190 is an enzyme that catalyzes both the condensation of two molecules of C5 dimethylallyl diphosphate (DMAPP) and the subsequent cyclization. CLDS was crystallized in the absence and the presence of the substrate DMAPP. Diffraction data were collected at a synchrotron source and the crystals diffracted to 2.00 and 1.73 Å resolution, respectively. The crystal obtained in the absence of DMAPP belonged to space group P212121, with unit-cell parameters a = 39.0, b = 87.5, c = 113.6 Å. The crystal obtained in the presence of DMAPP belonged to space group P1, with unit-cell parameters a = 46.9, b = 61.7, c = 82.2 Å, α = 74.0, β = 84.5, γ = 86.0°.

MISC

• 環状ペプチドの効率的な化学－酵素合成法

  松田研一, 脇本敏幸  Bioscience & Industry  81-  (6)  505  -508  2023/11
• ペニシリン結合タンパク質型チオエステラーゼを用いた環状ペプチドの効率的な化学– 酵素合成

  松田研一, 脇本敏幸  Peptide Newsletter Japan  129-  4  -7  2023/07
• 細菌のもつ多様なヒドラジン生合成経路の開拓

  松田研一  化学と工業  76-  (1)  017  -017  2023/01  [Not refereed][Invited]
  
• ペプチド環化反応を触媒する新しい酵素ファミリー「PBP-type TE」の発見と機能解析

  松田研一, 脇本敏幸  アグリバイオ  6-  (8)  734  -739  2022/07  [Not refereed][Invited]
  
• (研究教育の座右の銘)・趣味・(抱負)

  松田研一  ファルマシア  58-  (5)  465  2022/05  [Not refereed][Invited]
  
• 新規ペプチド環化酵素PBP-type TEの発見と機能解析

  松田研一, 脇本敏幸  ファインケミカル  2021/04
• A Tale of Penicillin-Binding Protein Specialized for Peptide Cyclization

  Kenichi Matsuda  Nature Research Chemistry Community - Behind the Paper  2020/05  [Not refereed][Not invited]
  
• Genome-mining of amino group carrier protein-mediated machinery led to the discovery of an unprecedented hydrazine-forming enzyme in bacteria.

  松田研一, 西山真  Journal of Japanese Biochemical Society  92-  (1)  130  -135  2020/02/05  [Not refereed][Not invited]
  
• バクテリアが有する新たな非リボソームペプチド環化酵素

  松田研一, 脇本敏幸  バイオサイエンスとインダストリー  77-  (4)  306‐307  2019/07/10  [Not refereed][Not invited]
  
• ペニシリン結合タンパク質によるペプチド環化 非リボソーム依存性ペプチド生合成における新規環化酵素の発見

  松田研一, 倉永健史, 脇本敏幸  ファルマシア(Web)  55-  (7)  650‐654(J‐STAGE)  2019  [Not refereed][Not invited]
  
• Genome Mining of Amino Group-Carrier Protein-Mediated Machinery: Insights into Biosynthesis of Unique Hydrazone Unit

  松田研一, 富田武郎, 志波優, 兼崎友, 吉川博文, 新家一男, 脇本敏幸, 葛山智久, 西山真  天然有機化合物討論会講演要旨集(Web)  59th-  2017
• Screening of secondary metabolites biosynthesized with novel amino acid carrier protein system

  Kenichi Matsuda, Fumihito Hasebe, Takeo Tomita, Yu Shiwa, Hirofumi Yoshikawa, Kazuo Shin-ya, Tomohisa Kuzuyama, Makoto Nishiyama  FASEB JOURNAL  28-  (1)  2014/04  [Not refereed][Not invited]
  

Presentations

• Exploration and biocatalytic application of enzymes in specialized metabolism  [Invited]

  Kenichi Matsuda

  日本薬学会第144年会（横浜） [IS01] 次世代薬学アジアシンポジウム ケミカルバイオロジー1  2024/03
• [S19-3] 天然物生合成酵素を活用した環状中分子の化学－酵素合成  [Invited]

  松田研一

  日本薬学会第144年会（横浜） [S19] 中分子創薬研究のフロンティア －中分子創薬に資する次世代分子技術－  2024/03
• シアノバクチン生合成におけるグアニジンビスプレニル化酵素の網羅的探索と機能解析

  藤田慧、山田惟人、松田研一、脇本敏幸

  日本薬学会第144年会（横浜）  2024/03
• ヒドラジン生合成に関わるN-水酸化酵素の系統解析と新規ヒドラジン化合物の同定

  中原 悠斗, Choirunnisa Atina, 有馬 陸, 松田 研一, 脇本 敏幸

  日本薬学会第144年会（横浜）  2024/03
• インドールN-アシル化によるペプチド環化機構

  丸山 広大, 松田 研一, 小谷 真也, 五十嵐 康弘, 脇本敏幸

  日本薬学会第144年会（横浜）  2024/03
• 二環性ペプチドの化学-酵素合成

  小野澤菜帆、小林 雅和、松田 研一、脇本 敏幸

  日本薬学会第144年会（横浜）  2024/03
• [30-411-am04] 非リボソームペプチド環化酵素を用いたラリアット型環状ペプチドの化学－酵素合成

  小林 雅和、松田 研一、脇本 敏幸

  日本薬学会第144年会（横浜）  2024/03
• 非リボソームペプチオ環化酵素を用いたhead-to-side chain型環状ペプチドの化学－酵素合成

  小林 雅和、松田 研一、脇本 敏幸

  日本農芸化学会2024年度大会  2024/03
• A New Family of Peptide Cyclases Enabled Streamlined Chemoenzymatic Synthesis of Cyclic Peptides  [Invited]

  Kenichi Matsuda, Toshiyuki Wakimoto

  2023 The 1st Taiwan-Japan Bilateral Symposium on Natural Products Biosynthesis  2023/12
• 有用な天然物生合成酵素の探索とその触媒利用  [Invited]

  松田研一

  9th BROGHT Symposium  2023/10
• Actinopyridazinone 生合成における複素環形成機構の解明

  有馬陸、秋山智子、松田研一、脇本敏幸

  第24回天然薬物の開発と応用シンポジウム  2023/10
• 二環性ペプチドの化学-酵素合成

  小野澤菜帆、小林 雅和、松田 研一、脇本 敏幸

  第24回天然薬物の開発と応用シンポジウム  2023/10
• 抗結核菌活性環状ヘキサペプチド wollamide 生合成における環化酵素 WolJの機能解析

  市原 凜太郎、小林 雅和、藤田 慧、松田 研一、脇本 敏幸

  第24回天然薬物の開発と応用シンポジウム  2023/10
• NRPS-PKSハイブリッド型天然物の生合成におけるα-ケトアミド形成機構に関する研究

  山田惟人, 福場淳生, 松田研一, 脇本敏幸

  第24回天然薬物の開発と応用シンポジウム  2023/10
• アルギニン選択的環状ペプチドビスプレニル化酵素の網羅的探索と機能解析

  藤田慧、松田研一、脇本敏幸

  第24回天然薬物の開発と応用シンポジウム  2023/10
• チロシンイソシアニド化酵素HzmAの機能解析

  丸山 広大, 井町 久美子, 松田 研一, 脇本敏幸

  第24回天然薬物の開発と応用シンポジウム  2023/10
• A New Family of Peptide Cyclases Enabled Streamlined Chemoenzymatic Synthesis of Cyclic Peptide

  Kenichi Matsuda, Masakazu Kobayashi, Kei Fujita, Toshiyuki Wakimoto

  The 23rd Symposium of the Society of Biocatalysis Japan  2023/09
• 窒素-窒素共有結合を含むヘテロ環の生合成機構の解明とその分光学的測定法の開発

  有馬陸、秋山智子、福士江里、松田研一、脇本敏幸

  第65回天然有機化合物討論会  2023/09
• 非リボソームペプチド環化酵素を利用した環状ペプチドの効率的合成法の開発

  小林雅和、市原凛太朗、藤田慧、松田研一、脇本敏幸

  第65回天然有機化合物討論会  2023/09
• NRPS-PKSハイブリッド型天然物の生合成におけるα-ketoamide形成機構に関する研究

  山田惟人, 福場淳生, 松田研一, 脇本敏幸

  日本生薬学会第69年会  2023/09
• 非リボソームペプチド環化酵素 WolJ を用いた抗結核菌活性環状ペプチドの構造展開

  市原 凜太郎、小林 雅和、藤田 慧、松田 研一、脇本 敏幸

  日本生薬学会第69年会  2023/09
• 二環性ペプチドの化学-酵素合成

  小野澤菜帆、小林 雅和、松田 研一、脇本 敏幸

  日本生薬学会第69年会  2023/09
• A New Family of Peptide Cyclases Enabled Streamlined Chemoenzymatic Synthesis of Cyclic Peptides

  Kenichi Matsuda, Masakazu Kobayashi, Kei Fujita, Toshiyuki Wakimoto

  3rd Japan-Switzerland-Germany Workshop on Biocatalysis and Bioprocess Development  2023/09
• チロシンイソシアニド化酵素HzmAの機能解析

  丸山 広大, 井町 久美子, 松田 研一, 脇本敏幸

  第37回放線菌学会大会  2023/09
• Actinopyridazinone生合成における特異な複素環形成機構の解明

  有馬陸、秋山智子、松田研一、脇本敏幸

  予知生合成科学2023年若手合宿勉強会  2023/08
• NRPS-PKSハイブリッド型天然物生合成におけるフラビン依存性酸化酵素によるα-ケトアミド形成

  山田惟人, 福場淳生, 松田研一, 脇本敏幸

  予知生合成科学2023年若手合宿勉強会  2023/08
• ハジマイシン生合成におけるイソシアニド合成酵素HzmAの機能解析

  丸山 広大, 井町 久美子, 松田 研一, 脇本敏幸

  予知生合成科学2023年若手合宿勉強会  2023/08
• アルギニンビスプレニル化酵素の探索と機能解析

  藤田慧、松田研一、脇本敏幸

  第55回若手ペプチド夏の勉強会  2023/08
• 非リボソームペプチド環化酵素WolJを用いた抗結核菌活性環状ペプチドWollamideの構造展開

  市原 凜太郎、小林 雅和、藤田 慧、松田 研一、脇本 敏幸

  第55回若手ペプチド夏の勉強会  2023/08
• Actinopyridazinone生合成における特異な複素環形成機構の解明

  有馬陸、秋山智子、松田研一、脇本敏幸

  第35回万有札幌シンポジウム  2023/07
• Streamlined Chemoenzymatic Synthesis of Cyclic Peptides by Non-ribosomal Peptide Cyclases

  Kenichi Matsuda, Masakazu Kobayashi, Kei Fujita, Toshiyuki Wakimoto

  Biotrans2023  2023/06
• アルギニンビスプレニル化酵素の探索と機能解析

  藤田慧、松田研一、脇本敏幸

  第15回化学生態学研究会  2023/06
• イソシアニド生合成酵素HzmAの機能解析

  丸山 広大, 井町 久美子, 松田 研一, 脇本敏幸

  第15回化学生態学研究会  2023/06
• イソシアニド生合成酵素HzmAの機能解析

  丸山 広大, 井町 久美子, 松田 研一, 脇本敏幸

  第47回日本生薬学会北海道支部例会  2023/05
• 二環性ペプチドの化学-酵素合成

  小野澤菜帆、小林 雅和、松田 研一、脇本 敏幸

  第47回日本生薬学会北海道支部例会  2023/05
• Streamlined chemoenzymatic synthesis of cyclic peptides by non-ribosomal peptide cyclases  [Not invited]

  Kenichi Matsuda, Masakazu Kobayashi, Kei Fujita, Toshiyuki Wakimoto

  NextGenBiocat 2023  2023/04
• Identification of the Gene Cluster Involved in Doubly Homologated Tyrosine Biosynthesis from Microcystis aeruginosa  [Not invited]

  Zhengyi Ling, Chin-Soon Phan, Jakia Jerin Mehjabin, Kenichi Matsuda, Prakoso Nurcahyo Iman, Taiki Umezawa, Toshiyuki Wakimoto, Tatsufumi Okino

  日本薬学会第143年会（札幌）  2023/03
• Carrier protein-mediated heterocyclization in actinopyridazinone biosynthesis  [Not invited]

  Kuga Arima, Satoko Akiyama, Kenichi Matsuda, Toshiyuki Wakimoto

  日本薬学会第143年会（札幌）  2023/03
• 非リボソームペプチド環化酵素WolJの基質選択性に関する研究  [Not invited]

  市原 凜太郎, 小林 雅和, 藤田 慧, 松田 研一, 脇本 敏幸

  日本薬学会第143年会（札幌）  2023/03
• イソシアニド生合成酵素HzmAの機能解析  [Not invited]

  丸山 広大, 井町 久美子, 松田 研一, 脇本 敏幸

  日本薬学会第143年会（札幌）  2023/03
• Actinopyridazinone生合成における特異な複素環形成機構の解明  [Not invited]

  有馬 陸, 秋山 智子, 松田 研一, 脇本 敏幸

  日本薬学会第143年会（札幌）  2023/03
• NRPS-PKSハイブリッド型天然物の生合成におけるα-ケトアミド形成を担う新規酸化酵素に関する研究  [Not invited]

  山田 惟人, 福場 淳生, 松田 研一, 脇本 敏幸

  日本薬学会第143年会（札幌）  2023/03
• 寛容な基質選択性を有するアルギニンビスプレニル化酵素AnzFの同定  [Not invited]

  藤田 慧, 松田 研一, 脇本 敏幸

  , 日本薬学会第143年会（札幌）  2023/03
• 非リボソームペプチド環化酵素を利用した環状ペプチドの効率的な化学-酵素合成法の開発  [Not invited]

  小林 雅和, 藤田 慧, 松田 研一, 脇本 敏幸

  日本薬学会第143年会（札幌）  2023/03
• 伝統水産発酵食品くさやから分離した放線菌Streptomyces diastaticus TUA-NKU25株の塩依存的Surugamide A生産と生合成遺伝子の特徴  [Not invited]

  鈴木 敏弘, 竹内 葵, 平田 朝陽, 手島 愛子, 植木 美羽, 松田 研一, 脇本 敏幸, 荒川 賢治, 石川 森夫

  日本農芸化学会2023年度大会  2023/03
• 寛容な基質選択性を有するアルギニンビスプレニル化酵素AnzFの同定  [Not invited]

  藤田 慧, 松田 研一, 脇本 敏幸

  日本農芸化学会2023年度大会  2023/03
• Actinopyridazinone生合成におけるキャリアタンパク質を介したジヒドロピリダジノン環形成機構の解明  [Not invited]

  有馬 陸, 秋山 智子, 松田 研一, 脇本 敏幸

  日本農芸化学会2023年度大会  2023/03
• STREAMLINED CHEMOENZYMATIC SYNTHESIS OF CYCLIC PEPTIDES BY NON-RIBOSOMAL PEPTIDE CYCLASES  [Not invited]

  Masakazu Kobayashi, Kei Fujita, Kenichi Matsuda, Toshiyuki Wakimoto

  International Conference on Natural Product Discovery and Development in the Genomic Era, SIMB  2023/01
• IDENTIFICATION OF ANZF, ARG-BISPRENYLTRANSFERASE WITH BROAD SUBSTRATE SELECTIVITY  [Not invited]

  Kei Fujita, Kenichi Matsuda, Toshiyuki Wakimoto

  International Conference on Natural Product Discovery and Development in the Genomic Era, SIMB 2023  2023/01
• EXPLORING THE HYDRAZINE BIOSYNTHETIC PATHWAYS IN BACTERIAL SECONDARY METABOLISM  [Not invited]

  Kenichi Matsuda, Kuga Arima, Satoko Akiyama, Yo Abe, Yuito Yamada, Toshiyuki Wakimoto

  International Conference on Natural Product Discovery and Development in the Genomic Era, SIMB  2023/01
• Exploring amine-modifying enzymes in bacterial hydrazine synthetic pathways  [Not invited]

  Kenichi Matsuda, Arima Kuga, Satoko Akiyama, Toshiyuki Wakimoto

  Amine Biocat 5.0  2022/11
• Identification of guanidine bis-prenyltransferase with broad substrate tolerance  [Not invited]

  Kei Fujita, Kenichi Matsuda, Toshiyuki Wakimoto

  The 59th Japanese Peptide Symposium  2022/10
• アルギニンビスプレニル化酵素の探索と機能解析

  藤田慧, 松田研一, 脇本敏幸

  第34回 万有札幌シンポジウム  2022/10
• Exploring the hydrazine biosynthetic pathways in bacteria  [Invited]

  Kenichi Matsuda, Kuga Arima, Satoko Akiyama, Kazuo Shin-ya, Makoto Nishiyama, Toshiyuki Wakimoto

  JNU-UTokyo Joint Seminar on Natural Product Biosynthesis  2022/09
• 細胞外⼩胞が⽣産誘導する放線菌由来新規抗菌性天然物の探索  [Not invited]

  本田拓⺒, 吉村彩, 中田隆介, 松田研一, 脇本敏幸

  第 36 回（2022 年度）⽇本放線菌学会⼤会  2022/09
• ジヒドロピリダジノン環含有天然物 actinopyridazinone A の⽣合成経路の解明  [Not invited]

  有馬 陸, 秋山 智子, 松田 研一, 脇本 敏幸

  第 36 回（2022 年度）⽇本放線菌学会⼤会  2022/09
• 天然物生合成におけるペプチド修飾反応に関する研究  [Not invited]

  松田研一

  日本生薬学会第68回年会  2022/09
• ジヒドロピリダジノン環含有天然物, actinopyridazinone Aの生合成機構の解明  [Not invited]

  有馬陸, 秋山智子, 松田研一, 脇本敏幸

  日本生薬学会第68回年会  2022/09
• 環状ペプチドを基質とするグアニジンビスプレニルトランスフェラーゼの機能解析  [Not invited]

  藤田慧, 松田研一, 脇本敏幸

  日本生薬学会第68回年会  2022/09
• α-ketoamide形成を担う新規酸化酵素の同定及び機能解析  [Not invited]

  山田惟人, 福場淳生, 松田研一, 脇本敏幸

  日本生薬学会第68回年会  2022/09
• 細菌が放出する細胞外小胞による二次代謝産物生産誘導に関する研究  [Not invited]

  吉村彩, 佐伯梨緒, 中田隆介, 冨本将汰, 松田研一, 脇本敏幸

  第64回天然有機化合物討論会  2022/09
• Exploring the hydrazine biosynthetic pathways in bacteria  [Not invited]

  Kenichi Matsuda

  Sapporo Summer Seminar on Natural Product Biosynthesis  2022/08
• PBP型チオエステラーゼSurEによるペプチドライゲーション反応  [Not invited]

  市原凜太郎, 小林雅和, 松田研一, 脇本敏幸

  日本生薬学会第46回北海道支部例会  2022/05
• 窒素―窒素共有結合形成酵素の機能解析  [Not invited]

  伊藤楓, 有馬陸, 松田研一, 脇本敏幸

  日本生薬学会第46回北海道支部例会  2022/05
• 非リボソームペプチド環化酵素SurEの基質選択性の合理的改変  [Not invited]

  日本薬学, 名古

  2022/03
• NRPS-PKSハイブリッド型天然物の生合成におけるα-ketoamide形成機構に関する研究  [Not invited]

  山田 惟人, 福場 淳生, 松田 研一, 脇本 敏幸

  日本薬学会第142年会（名古屋）  2022/03
• 環状ペプチドを基質とするグアニジンプレニル化酵素AgcFの機能解析  [Not invited]

  藤田 慧, 松田 研一, 脇本 敏幸

  日本薬学会第142年会（名古屋）  2022/03
• 特異なdihydropyridazinone環を有する新規天然物actinopyridazinone Aに関する研究  [Not invited]

  有馬 陸, 秋山 智子, 松田 研一, 脇本 敏幸

  日本薬学会第142年会（名古屋）  2022/03
• ペプチド環化酵素ファミリーPBP-type TEの発見・機能解析・応用  [Invited]

  松田研一

  日本薬学会第142年会 一般シンポジウム「[S08] タンパク質工学による創薬化学の新展開」  2022/03
• PBP-type TE, a new family of offloading cyclase in biosynthesis of non-ribosomal macrolactam

  Kenichi Matsuda, Rui Zhai, Takahiro Mori, Masakazu Kobayashi, Ayae Sano, Ikuro Abe, Toshiyuki Wakimoto

  Pacifichem 2021  2021/12
• Enzymatic basis of guanidine bis-prenylation in argicyclamide biosynthesis  [Not invited]

  Kenichi Matsuda, Chin-Soon Phan, Nandani Balloo, Kei Fujita, Okino Tatsufumi, Toshiyuki Wakimoto

  第58回ペプチド討論会  2021/10
• 非リボソームペプチド生合成における新規ペプチド環化酵素の発見と機能解析  [Invited]

  松田研一

  第23回天然薬物の開発と応用シンポジウム  2021/10
• ゲノム情報と比色法を利用した稀少天然物の開拓  [Invited]

  松田研一

  日本生薬学会第67回年会 若手シンポジウム  2021/09
• 窒素－窒素結合含有天然物のゲノムマイニング  [Not invited]

  松田研一, 有馬陸, 秋山智子, 阿部葉, 城内航, 新家一男, 脇本敏幸

  第63回天然有機化合物討論会  2021/09
• Argicyclamide revealed enzymatic basis for guanidine bis-prenylation  [Not invited]

  Matsuda, K, Phan, C.-S, Balloo, N, Fujita, K, Okino, T, Wakimoto, T

  第53回若手ペプチド夏の勉強会  2021/08
• A marine-derived biocatalyst for cyclic peptide production  [Invited]

  Kenichi Matsuda

  The 4th international symposium on marine and fisheries research  2021/07
• 海洋放線菌に見出した新規ペプチド環化酵素ファミリーの機能解析と応用可能性  [Invited]

  松田研一

  第21回マリンバイオテクノロジー学会ミニシンポジウム（若手の会）  2021/05
• 新規ペプチド環化酵素の発見と機能解析  [Invited]

  松田研一

  第3回「生体適合化学の進歩」インタラクティブフォーラム  2021/04
• A new off-loading cyclase in non-ribosomal peptide biosynthesis  [Not invited]

  Matsuda, K, Wakimoto, T

  2nd German-Japanese Symposium on Natural Product Biosynthesis  2020/04
• trans-TE NRPS の発見と機能改変  [Invited]

  松田研一

  若手研究者のための有機化学札幌セミナー  2019/11
• Penicillin-binding protein-type thioesterases; scope, limitation and its application  [Invited]

  Kenichi Matsuda

  13th Australian Peptide Conference  2019/09
• Identification of a new family of offloading cyclase in biosynthesis of non-ribosomal peptide  [Invited]

  Kenichi Matsuda

  7th Modern Solid Phase Peptide Synthesis & Its Application Symposium  2019/09
• 非リボソームペプチドの環化反応を触媒するペニシリン結合タンパク質ファミリーの発見と機能解析  [Invited]

  松田研一

  新学術領域生合成リデザイン特別講演会  2019/06
• ペニシリン結合タンパク質による非リボソームペプチドの環化反応  [Invited]

  松田研一

  日本薬学会、第139年会, シンポジウムS43 「生体分子骨格リデザインで挑む次世代創薬研究」  2019/03
• ペプチド環化酵素SurEの生産菌が有する新規ペプチド環化酵素FalKOの機能解析

  市原 凜太郎、松田 研一、脇本 敏幸

  第48回日本生薬学会北海道支部例会

Association Memberships

• 日本化学会   THE JAPANESE SOCIETY OF PHARMACOGNOSY   SOCIETY FOR ACTINOMYCETES JAPAN   JAPAN SOCIETY FOR BIOSCIENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY   日本薬学会   

Research Projects

• 新規窒素代謝で実現するバイオヒドラジン生産

  JST：2023創発的研究支援事業

  Date (from‐to) : 2024 -2031
• 微生物－酵素触媒複合系によるバイオヒドラジン生産

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2024/04 -2027/03 

  Author : 松田 研一
• 複雑修飾中分子の固相化学酵素合成

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2023/06 -2027/03 

  Author : 松田 研一
• 新規ペプチド修飾酵素の機能拡張による大環状複雑骨格の創出

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Transformative Research Areas (A)

  Date (from‐to) : 2022/06 -2027/03 

  Author : 脇本 敏幸, 松田 研一
• 感染症治療薬の新モダリティー天然物2.0

  日本医療研究開発機構(AMED)：AMED-CREST

  Date (from‐to) : 2022 -2027 

  Author : 浅井禎吾
• 短鎖環状ペプチドの酵素・生物合成

  科学技術振興機構：戦略的な研究開発の推進 戦略的創造研究推進事業 ACT-X 加速フェーズ

  Date (from‐to) : 2023/04 -2024/03 

  Author : 松田 研一

   

  短鎖環状ペプチドは優れた代謝安定性・組織移行性を示します。本研究では、短鎖環状ペプチドの合成に特化した新規なペプチド環化酵素ファミリーに着目し、その機能解析に基づく論理的な酵素改良を行い、生体触媒として開発すると共に、本酵素の合成生物学的利用法を提案します。これによりこれまで効率的な合成が困難であった短鎖環状ペプチドを、精度よく安定してかつ大量に合成できる環境調和性の技術の開発を目指します。
• 複雑修飾ペプチドのフロー生体触媒合成

  公益財団法人 テルモ生命科学振興財団：2022 年度 Ⅲ研究助成金

  Date (from‐to) : 2023/04 -2024/03
• 合成終盤における酵素的構造多様化を基盤とする複雑修飾ペプチド創成プラットフォーム

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

  Date (from‐to) : 2022/04 -2024/03 

  Author : 松田 研一
• PBP-type TEを基軸とした環状ペプチドの新規供給法の確立

  公益財団法人 内藤記念科学振興財団：次世代育成支援研究助成

  Date (from‐to) : 2020/04 -2023/03 

  Author : 松田研一
• PBP type-TEのペプチド環化触媒能の解明と環状ペプチドの多様性拡張

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

  Date (from‐to) : 2019/04 -2022/03 

  Author : Matsuda Kenichi

   

  SurE, a novel peptide cyclase involved in the biosynthesis of nonribosomal macrolactams produced by actinomycetes, was analyzed to elucidate its substrate selectivity and its structural basis; biochemical and structural comparison between SurE and two homologous enzymes was performed to clarify the structure that generates differences in substrate selectivity. Based on the findings obtained, we succeeded in logically modifying the substrate selectivity of the enzyme. Furthermore, we investigated the synthesis scheme of the enzyme substrate and established a highly efficient synthetic method. The modified solid phase peptide synthesis combined with sequential enzymatic cyclization realized seamless chemoenzymatic synthesis of cyclic peptides.
• 短鎖環状ペプチドの酵素・生物合成

  戦略的な研究開発の推進 戦略的創造研究推進事業 ACT-X

  Date (from‐to) : 2020 -2022 

  Author : 松田 研一

   

  短鎖環状ペプチドは優れた代謝安定性・組織移行性を示します。本研究では、短鎖環状ペプチドの合成に特化した新規なペプチド環化酵素ファミリーに着目し、その機能解析に基づく論理的な酵素改良を行い、生体触媒として開発すると共に、本酵素の合成生物学的利用法を提案します。これによりこれまで効率的な合成が困難であった短鎖環状ペプチドを、精度よく安定してかつ大量に合成できる環境調和性の技術の開発を目指します。
• PBP type-TEによる環状ペプチドの化学・生物生産

  上原記念生命科学財団：研究奨励金

  Date (from‐to) : 2020/04 -2021/03 

  Author : 松田研一
• PBP type-TEを基軸とする環状ペプチドの革新的生産法の確立

  北海道大学：若手研究加速事業

  Date (from‐to) : 2019/09 -2020/03
• 新規ペプチド環化酵素ファミリーPBP-type TE における特異性発現メカニズムの解明

  第一三共生命科学研究振興財団：研究助成

  Author : 松田研一
• ペプチド環化酵素PBP-type TEの基質選択性発現メカニズムの解明と改変

  住友財団：2020年度 基礎科学研究助成

  Author : 松田研一

Industrial Property Rights

• 特願2022-24966:環状ペプチドの効率的な化学－酵素合成方法  2022年/02/21

  脇本敏幸, 松田研一, 小林雅和  国立大学法人北海道大学
• 特願PCT/JP2022/004501:新規プレニル化酵素  2022年/02/04

  脇本敏幸, 沖野龍文, 松田研一, パンチンスン  国立大学法人北海道大学
• 特願2021-157054:酵素を用いたペプチドライゲーション  2021年/09/27

  脇本敏幸, 松田研一, 小林雅和  国立大学法人北海道大学
• 特願2018-89287:ペプチド類の大環状化酵素  2018年/05/07

  脇本敏幸, 倉永健史, 松田研一
• 特願2021-109058:化合物、その製造方法、抗菌剤及び銅キレート剤医薬  

  高田雅親, 砂原博文, 脇本敏幸, 松田研一  株式会社村田製作所, 国立大学法人北海道大学
• 特願2021-109057:銅キレート剤、抗がん剤及びウィルソン病の予防又は治療剤  

  高田雅親, 砂原博文, 脇本敏幸, 松田研一  株式会社村田製作所, 国立大学法人北海道大学