Curriculum Vitaes

Makoto Hashimoto

  (橋元 誠)

Profile Information

Affiliation
-, Faculty of Pharmacy Department of Pharmaceutical Sciences, Musashino University
Degree
Master (Agriculture)(Tokyo University of Agriculture and Technology)

J-GLOBAL ID
200901074534035987
researchmap Member ID
5000023937

Committee Memberships

 1

Papers

 10
  • Makoto Hashimoto, Susumu Watari, Takaaki Taguchi, Kazuki Ishikawa, Takuya Kumamoto, Susumu Okamoto, Koji Ichinose
    Angewandte Chemie (International ed. in English), Dec 2, 2022  
    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, Jun 15, 2022  
    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, May 25, 2020  
  • 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, May 25, 2020  Peer-reviewed
    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, Mar 2, 2020  

Misc.

 12

Presentations

 53

Teaching Experience

 7

Research Projects

 5

Academic Activities

 2