研究者業績

橋元 誠

ハシモト マコト  (Makoto Hashimoto)

基本情報

所属
武蔵野大学 薬学部 薬学科 講師
学位
博士(農学)(東京農工大学大学院連合農学研究科)

J-GLOBAL ID
200901074534035987
researchmap会員ID
5000023937

委員歴

 1

論文

 10
  • Makoto Hashimoto, Susumu Watari, Takaaki Taguchi, Kazuki Ishikawa, Takuya Kumamoto, Susumu Okamoto, Koji Ichinose
    Angewandte Chemie (International ed. in English) 2022年12月2日  
    A plethora of dimeric natural products exist with diverse chemical structures and biological activities. A major strategy for dimerization is aryl coupling reactions catalyzed by cytochrome P450 or laccase. Actinorhodin (ACT) from Streptomyces coelicolor has a dimeric pyranonaphthoquinone structure connected by a C-C bond. Here, we identified a NmrA-family dimerizing enzyme, ActVA-ORF4, and a cofactor independent oxidase, ActVA-ORF3, both involved in the last step of ACT biosynthesis. ActVA-ORF4 is a unique  NAD(P)H-dependent enzyme that catalyzes the inter-molecular C-C bond formation using 8-hydroxydihydrokalafungin (DHK-OH) as the sole substrate. On the other hand, ActVA-ORF3 was found to be a quinone-forming enzyme that produces the coupling substrate, DHK-OH, and the final product, ACT. Consequently, the functional assignment of all essential enzymes in ACT biosynthesis was completed, which would be a landmark in our understanding of the entire biosynthetic pathway for one of the best-known model natural products, ACT.
  • Kazuki Ishikawa, Makoto Hashimoto, Kunpei Komatsu, Takaaki Taguchi, Susumu Okamoto, Koji Ichinose
    Bioorganic & medicinal chemistry letters 66 128727-128727 2022年6月15日  
    Actinorhodin (ACT) is a benzoisochromanequinone antibiotic produced by Streptomyces coelicolor A3(2), which has served as a favored model organism for comprehensive studies of antibiotic biosynthesis and its regulation. (S)-DNPA undergoes various modifications as an intermediate in the ACT biosynthetic pathway, including enoyl reduction to DDHK. It has been suggested that actVI-ORF2 encodes an enoyl reductase (ER). However, its function has not been characterized in vitro. In this study, biochemical analysis of recombinant ActVI-ORF2 revealed that (S)-DNPA is converted to DDHK in a stereospecific manner with NADPH acting as a cofactor. (R)-DNPA was also reduced to 3-epi-DDHK with the comparable efficacy as (S)-DNPA, suggesting that the stereospecificity of ActVI-ORF2 was not affected by the stereochemistry at the C-3 of DNPA. ActVI-ORF2 is a new example of a discrete ER, which is distantly related to known ERs according to phylogenetic analysis.
  • Isao Fujii, Makoto Hashimoto, Kaori Konishi, Akiko Unezawa, Haruka Sakuraba, Kenta Suzuki, Harue Tsushima, Miho Iwasaki, Satsuki Yoshida, Akane Kudo, Rina Fujita, Aika Hichiwa, Koharu Saito, Takashi Asano, Jun Ishikawa, Daigo Wakana, Yukihiro Goda, Ayumi Watanabe, Mamoru Watanabe, Yui Masumoto, Junichiro Kanazawa, Hajime Sato, Masanobu Uchiyama
    Angewandte Chemie 132(22) 8542-8548 2020年5月25日  
  • Isao Fujii, Makoto Hashimoto, Kaori Konishi, Akiko Unezawa, Haruka Sakuraba, Kenta Suzuki, Harue Tsushima, Miho Iwasaki, Satsuki Yoshida, Akane Kudo, Rina Fujita, Aika Hichiwa, Koharu Saito, Takashi Asano, Jun Ishikawa, Daigo Wakana, Yukihiro Goda, Ayumi Watanabe, Mamoru Watanabe, Yui Masumoto, Junichiro Kanazawa, Hajime Sato, Masanobu Uchiyama
    Angewandte Chemie (International ed. in English) 59(22) 8464-8470 2020年5月25日  査読有り
    Shimalactones A and B are neuritogenic polyketides possessing characteristic oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene ring systems that are produced by the marine fungus Emericella variecolor GF10. We identified a candidate biosynthetic gene cluster and conducted heterologous expression analysis. Expression of ShmA polyketide synthase in Aspergillus oryzae resulted in the production of preshimalactone. Aspergillus oryzae and Saccharomyces cerevisiae transformants expressing ShmA and ShmB produced shimalactones A and B, thus suggesting that the double bicyclo-ring formation reactions proceed non-enzymatically from preshimalactone epoxide. DFT calculations strongly support the idea that oxabicyclo-ring formation and 8π-6π electrocyclization proceed spontaneously after opening of the preshimalactone epoxide ring through protonation. We confirmed the formation of preshimalactone epoxide in vitro, followed by its non-enzymatic conversion to shimalactones in the dark.
  • Makoto Hashimoto, Takaaki Taguchi, Kazuki Ishikawa, Ryuichiro Mori, Akari Hotta, Susumu Watari, Kazuaki Katakawa, Takuya Kumamoto, Susumu Okamoto, Koji Ichinose
    ChemBioChem 21(5) 574-574 2020年3月2日  

MISC

 12

講演・口頭発表等

 53
  • 橋元誠, 小松治彦, 小曽根郁子, 川出洋, 安部浩, 夏目雅裕
    日本放線菌学会大会講演要旨集 2003年6月26日
  • M Hashimoto, T Kondo, Kozone, I, H Kawaide, H Abe, M Natsume
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 2003年4月 TAYLOR & FRANCIS LTD
    Respectively, exogenous pamamycin-607 and A-factor restored or stimulated aerial mycelium formation in 30 (67%) and 6 (13%) of 45 Streptomyces strains, and both restored or stimulated it in 5 strains (11%). Pamamycin-607 production was detected in 3 of those strains that responded to pamamycin-607. These findings indicate that pamamycin-607 acts on the common regulatory system for aerial mycelium formation in Streptomyces spp. but is not a universal autoregulator. Increased or decreased antibacterial production occurred in 5 strains in association with aerial mycelium formation by pamamycin-607 or A-factor.
  • 橋元誠, 小松治彦, 小曽根郁子, 川出洋, 安部浩, 夏目雅裕
    日本農芸化学会大会講演要旨集 2003年3月5日

担当経験のある科目(授業)

 7

共同研究・競争的資金等の研究課題

 5

学術貢献活動

 2