Chemical Genomics Research Group

Identification of novel small molecular ligands is essential to understand diverse biological phenomena and to control the biological systems by chemical methods. This project focuses on the development of useful molecular ligands that are expected to contribute to an advance in environmental and resource sciences by employing chemical libraries that consist of microbial metabolites and/or synthetic compounds. In particular, we search into novel active compounds by constructing a variety of phenotypic screening systems using genetically modified animal, plant and yeast cells, and in vitro screening systems using various target proteins that include enzymes for metabolism and epigenetics. In addition, we construct new platforms for developing high throughput screening systems. Our goal is to identify and provide unique molecular ligands that are useful for chemical biology research aiming at exploiting new area of environmental and resource sciences.

Research Fields

Chemistry / Biology & Biochemistry / Molecular Biology & Genetics / Pharmacology & Toxicology / Microbiology

Research Subjects

• Basic and applied studies on development of drug screening systems for controling nitrogen metabolism
• Development of screening systems for inhibitors of energy metabolism and epigenetics
• Chemical biology for establishment of platforms for advanced high throughput screening systems

Publications

1. Fujishiro, S., Dodo, K., Iwasa, E., Teng, Y., Sohtome, Y., Hamashima, Y., Ito, A., Yoshida, M., Sodeoka, M.
   “Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: Reducing cytotoxicity by structural simplification.“
   Bioorg. Med. Chem. Lett. 23(3):733-6. doi: 10.1016/j.bmcl.2012.11.087, 2013.
2. Takahashi, M., Takemoto, Y., Shimazu, T., Kawasaki, H., Tachibana, M., Shinkai, Y., Takagi, M., Shin-Ya, K., Igarashi, Y., Ito, A., and Yoshida, M.
   “Inhibition of histone H3K9 methyltransferases by gliotoxin and related epipolythiodioxopiperazines.“
   J Antibiot (Tokyo). ;65(5):263-5. doi: 10.1038/ja.2012.6, 2012.
3. Ito, T., Umehara, T., Sasaki, K., Nakamura, Y., Nishino, N., Terada, T., Shirouzu, M., Padmanabhan, B., Yokoyama, S., Ito, A., Yoshida, M.
   “Real-time imaging of histone H4K12-specific acetylation determines the modes of action of histone deacetylase and bromodomain inhibitors.“
   Chem. Biol. 18(4):495-507. doi: 10.1016/j.chembiol.2011.02.009, 2011.
4. Islam, N. M., Kato, T., Nishino, N., Kim, H.-J., Ito, A., and Yoshida, M.
   “Bicyclic peptides as potent inhibitors of histone deacetylases: Optimization of alkyl loop length.“
   Bioorg. Med. Chem. Lett., 20: 997-999, 2010.
5. Matsuyama, A. and Yoshida, M.
   “Systematic cloning of an ORFeome using the gateway system.“
   Methods Mol. Biol., 577: 11-24, 2009.
6. Fukuda, I., Ito, A., Uramoto, M., Saitoh, H., Kawasaki, H., Osada, H., and Yoshida, M.
   “Kerriamycin B inhibits protein SUMOylation. “
   J. Antibiot (Tokyo). 62: 221-224, 2009.
7. Fukuda, I., Ito, A., Hirai, G., Nishimura, S., Kawasaki, H., Saitoh, H., Kimura, K., Sodeoka, M., and Yoshida, M.
   “Ginkgolic acid Inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate“
   Chem. Biol. 16: 133-140, 2009.
8. Nishino, N., Shivashimpi, G. M., Soni, P. B., Bhuiyan, M. P. I., Kato, T., Maeda, S., Nishino, T. G., and Yoshida, M.
   “Interaction of aliphatic cap group in inhibition of histone deacetylases by cyclic tetrapeptides.“
   Bioorg. Med. Chem., 16: 437-445, 2008.
9. Yashiroda, Y., Okamoto, R., Hatsugai, K., Takemoto, Y., Goshima, N., Saito, T., Hamamoto, M., Sugimoto, Y., Osada, H., Seimiya, H., and Yoshida, M.
   “A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor.“
   Biochem. Biophys. Res. Commun., 394: 569-573, 2010.
10. Yashiroda, Y., Matsuyama, A., and Yoshida, M.
    “New insights into chemical biology from ORFeome libraries. “
    Curr. Opin. Chem. Biol., 12: 55-59, 2008.