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)

概要

論文の詳細を見る
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.
天然有機化合物討論会の論文
2001-09-01

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)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク