微生物代謝物からの医薬品探索研究

抄録

The microbial screening is an approach for discovering medicines out of microbial metabolites. The natural products (microbial metabolites) are known to possess very unique and complicated structure that could not be imagined. In addition, many of them also have highly potent and selective (specific) biological activities. This report focuses on the feature and present situation of microbial screening in drug discovery field. Firstly, the recent study and development on antitumor antibiotics, duocarmyicins (related compounds) and calicheamicin γ₁^IIthat indicate extraordinary potent activity, are reviewed. Next, the biochemical and pharmacological study on KS-505a (C 40 tetraterpenoid) produced by Streptomyces argenteolus, a PDE 1 (calcium/calmodulin-dependent phosphodiesterase) isoform selective inhibitor, is presented. The relationship between the microbial screening and recent “chemical biology” or “chemical genetics” approach is also discussed, using for examples, the mode of action of rapamycin and stem cell-based medicine. Finally, the basic strategy in microbial screening (method, target diseases etc.) is described.