Carrier Protein Mediated Formation of the Dihydropyridazinone Ring in Actinopyridazinone Biosynthesis

  • Kuga Arima
    Faculty of Pharmaceutical Sciences Hokkaido University Kita 12, Nishi 6, Kita-ku Sapporo 060-0812 Japan
  • Satoko Akiyama
    Faculty of Pharmaceutical Sciences Hokkaido University Kita 12, Nishi 6, Kita-ku Sapporo 060-0812 Japan
  • Kazuo Shin‐ya
    National Institute of Advanced Industrial Science and Technology (AIST) Tokyo 135-0064 Japan
  • Kenichi Matsuda
    Faculty of Pharmaceutical Sciences Hokkaido University Kita 12, Nishi 6, Kita-ku Sapporo 060-0812 Japan
  • Toshiyuki Wakimoto
    Faculty of Pharmaceutical Sciences Hokkaido University Kita 12, Nishi 6, Kita-ku Sapporo 060-0812 Japan

書誌事項

公開日
2023-06-06
資源種別
journal article
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/anie.202305155
  • 10.1002/ange.202305155
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>Heterocycles with nitrogen‐nitrogen (N−N) bonds are privileged building blocks of synthetic drugs. They are also found in natural products, although the biosynthetic logic behind them is poorly understood. Actinopyridazinones produced by <jats:italic>Streptomyces</jats:italic> sp. MSD090630SC‐05 possess unique dihydropyridazinone rings that have been studied as core nuclei in several approved synthetic therapeutics. Herein, we performed gene knockouts and in vitro biochemical experiments to elucidate the major steps in actinopyridazinone biosynthesis, including the unprecedented carrier protein mediated machinery for dihydropyridazinone formation.</jats:p>

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