Antibiotics Laboratory

Small molecules produced by microorganisms have diversity in chemical structures and biological activities. The Antibiotics Laboratory is focusing on the isolation of new compounds that regulate the mammalian cell function from microbial metabolites. Cellular factors involved in proliferation, differentiation and apoptosis in mammalian cells are molecular targets to be inhibited by the chemical compounds. The compounds isolated from microorganisms are deposited in the newly established Natural Products Depository RIKEN (NPDepo), which makes chemical libraries. The laboratory is also devoted to the cloning of biosynthetic gene clusters of microbial secondary metabolites, the investigation of the molecular interaction between small molecules and their binding proteins, and proteomic analyses of drug targets. The research will provide the biochemical tools to investigate the complex biochemical processes of the mammalian cell functions and also establish the foundation for developing new medicines such as antitumor agents.

Research Subjects

• Microbiological and chemical approach for exploitation of novel bioprobes.
• Identification of molecular targets of bioprobes.
• Mining and functional analysis of molecular targets.

Publications

1. T. Motoyama T, T. Hayashi, H. Hirota, M. Ueki, H. Osada:
   "Terpendole E, a Kinesin Eg5 Inhibitor, Is a Key Biosynthetic Intermediate "
   Chemistry & Biology, 19 (12): 1611-1619, (2012)
2. Y. Futamura, M. Kawatani, S. Kazami, K. Tanaka, M. Muroi, T. Shimizu, K. Tomita, N. Watanabe, H. Osada:
   "Morphobase, an Encyclopedic Cell Morphology Database, and Its Use for Drug Target Identification,"
   Chemistry & Biology, 19 (12): 1620-1630, (2012)
3. M.M.G. Khan, S. Simizu , T. Suzuki, A. Masuda, M. Kawatani, M. Muroi, N. Dohmae, H. Osada.:
   "Protein disulfide isomerase-mediated disulfide bonds regulate the gelatinolytic activity and secretion of matrix metalloproteinase-9."
   Exp Cell Res, 318(8): 904-914 (2012)
4. S. Kazami, T. Usui, H. Osada.:
   "Actin stress fiber retraction and aggresome formation is a common cellular response to actin toxins."
   Biosci Biotechnol Biochem. 75: 1853-1855 (2011)
5. S. Panthee, S. Takahashi, H. Takagi, T. Nogawa, E. Oowada, M. Uramoto H. Osada:
   "Furaquinocins I and J: novel polyketide isoprenoid hybrid compounds from Streptomyces reveromyceticus SN-593."
   The Journal of Antibiotics 64, 509-513 (2011)
6. M.M.G. Khan, S. Simizu, N.S. Lai, M. Kawatani, T. Shimizu, H. Osada:
   "Discovery of a small molecule PDI inhibitor that inhibits reduction of HIV-1 envelope glycoprotein gp120"
   ACS Chem. Biol., 6, 245-251 (2011)
7. A.M. Ryden, C. Ruyter-Spira, R. Litjens, S. Takahashi, W. Quax, H. Osada, H. Bouwmeester, O. Kayser:
   "Molecular cloning and characterization of a broad substrate terpenoid oxidoreductase from Artemisia annua."
   Plant Cell Physiol., 51, 1219-1228 (2010)
8. L.. Lindqvist, F. Robert, W. Merrick, H. Kakeya, C. Frasr, H. Osada, J. Pelletier:
   "Inhibition of translation by cytotrienin A--a member of the ansamycin family"
   RNA, 16, 2404-2413 (2010)