1 脱水素型環状ジペプチド生合成酵素による生理活性物質生産(口頭発表の部)

• 神崎 浩

  岡山大院自然科学

• 柳澤 恵広

  岡山大農

• 赤澤 和美

  岡山大農

• 池田 万里

  岡山大農

• 森本 篤史

  岡山大農

• 仁戸田 照彦

  岡山大機器分析

書誌事項

タイトル別名

• 1 Production of Bioactive Compounds by Biosynthetic Enzymes of Dehydro Cyclic Dipeptides

抄録

Cyclic dipeptides (CDPs, diketopiperazines) and their derivatives are widely distributed in nature as secondary metabolites. Although some of dehydro-CDPs are known as cell cycle inhibitors, their effective syntheses have not been reported. We found that Streptomyces albulus KO23, an albonoursin-producing actinomycete, had a biosynthetic pathway from cyclo (Leu-Phe) to albonoursin, cyclo (ΔLeu-ΔPhe) by the fed-batch culture and the resting-cell experiments. And this enzyme activity was found to be effectively extracted in the cell-free extract of this actinomycete. This is the first report for the dehydrogenation of amino acid residues at α,β-positions in CDPs. Furthermore, this enzyme system enables us to synthesize several didehydro- and tetradehydro-CDPs from the corresponding CDPs. Among dehydro-CDPs prepared, the tetradehydro-CDPs exhibited cytotoxicity, while the didehydro-CDPs had no activity, indicating that dehydrogenation at α,β-positions of both amino acid residues in CDPs is required for cytotoxicity. Based on the above results, we speculated that a tetradehydro-CDP prepared from a didehydro-CDP exhibiting cytotoxicity might be a potent cytotoxic compound. Dehydrophenylahistin synthesized by this enzyme system from (-)-phenylahistin, which was recently reported to be a new cell cycle inhibitor, exhibited 1000 times higher inhibitory activity toward the first cleavage of sea urchin embryo than (-)-phenylahistin, and thus, would be a promising lead compound for antitumor agents.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 43 (0), 1-5, 2001

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390282681056094848
• NII論文ID: 110006682046
• DOI: 10.24496/tennenyuki.43.0_1
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可