Natural Product Biosynthesis Research Unit

Microorganism such as actinomycetes and filamentous fungi is a rich repository of valuable secondary metabolite. The understanding of biosynthetic mechanism is important to utilize microbial metabolites efficiently. Therefore we elucidate a key reaction of biosynthetic pathway by genetic and biochemical methods. We diversify microbial metabolites by modifying gene cluster and pathway engineering. In addition to the utilization of transcriptional regulators, we develop novel methods of activating biosynthetic gene cluster by small molecules, and create natural products. We construct microbial biosynthetic platform and efficiently produce valuable natural products using genetic resources from nature.

Research Fields

Chemistry / Biology & Biochemistry / Molecular Biology & Genetics / Microbiology / Multidisciplinary

Research Subjects

• Elucidation of biosynthetic mechanism of microbial secondary metabolite
• Production of natural products by gene activation
• Construction of biosynthetic platform and creation of valuable compounds

Publications

1. T. Nogawa, S. Takahashi, A. Okano, M. Kawatani, M. Uramoto, T. Saito, and H. Osada.:
   "Spirotoamides A and B, novel 6,6-spiroacetal polyketides isolated from a microbial metabolite fraction library."
   J. Antibiot., 65, 123-128 (2012)
2. S. Takahashi, A. Toyoda, Y. Sekiyama, H. Takagi, T. Nogawa, M. Uramoto, R. Suzuki, H. Koshino, T. Kumano, S. Panthee, T. Dairi, J. Ishikawa, H. Ikeda, Y. Sakaki, and H. Osada.:
   "Reveromycin A biosynthesis uses RevG and RevJ for stereospecific spiroacetal formation."
   Nat. Chem. Biol., 7, 461-468 (2011)
3. S. Panthee, S. Takahashi, H. Takagi, T. Nogawa, E. Oowada, M. Uramoto, and H. Osada.:
   "Furaquinocins I and J: Novel polyketide isoprenoid hybrid compounds from Streptomyces reveromyceticus SN-593."
   J. Antibiot., 64, 509-513 (2011)
4. N. Kato, H. Suzuki, H. Takagi, M. Uramoto, S. Takahashi, and H. Osada.:
   "Gene disruption and biochemical characterization of verruculogen synthase of Aspergillus fumigates."
   ChemBioChem, 12, 711-714 (2011)
5. N. Kato, M. Tokuoka, Y. Shinohara, M. Kawatani, M. Uramoto, Y. Seshime, I. Fujii, K. Kitamoto, T. Takahashi, S. Takahashi, Y. Koyama, and H. Osada.:
   "Genetic safeguard against mycotoxin cyclopiazonic acid production in Aspergillus oryzae."
   ChemBioChem, 12, 1376-1382 (2011)
6. H. Takayama, S. Takahashi, H. Osada, Y. Iwabuchi, and N. Kanoh.:
   "Detection of cytochrome P450 substrates using small-molecule droplet array on NADH-immobilized solid surface."
   ChemBioChem, 12, 2748-2752 (2011)
7. S. Takahashi, H. Takagi, A. Toyoda, M. Uramoto, T. Nogawa, M. Ueki, Y. Sakaki, and H. Osada.:
   "Biochemical characterization of a novel indole prenyltransferase from Streptomyces sp. SN-593."
   J. Bacteriol., 192, 2839-2851 (2010)
8. N. Kato, H. Suzuki, H. Takagi, Y. Asami, H. Kakeya, M. Uramoto, T. Usui, S. Takahashi, Y. Sugimoto, and H. Osada.:
   "Identification of cytochrome P450s required for fumitremorgin biosynthesis in aspergillus fumigatus."
   ChemBioChem, 10, 920-928 (2009)