Carrier Protein Mediated Formation of the Dihydropyridazinone Ring in Actinopyridazinone Biosynthesis.


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
17 07 2023
Historique:
received: 12 04 2023
medline: 12 7 2023
pubmed: 17 5 2023
entrez: 17 5 2023
Statut: ppublish

Résumé

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 Streptomyces 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.

Identifiants

pubmed: 37194491
doi: 10.1002/anie.202305155
doi:

Substances chimiques

Carrier Proteins 0
Biological Products 0
Nitrogen N762921K75

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202305155

Informations de copyright

© 2023 Wiley-VCH GmbH.

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Auteurs

Kuga Arima (K)

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.

Satoko Akiyama (S)

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.

Kazuo Shin-Ya (K)

National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, 135-0064, Japan.

Kenichi Matsuda (K)

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.

Toshiyuki Wakimoto (T)

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.

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Classifications MeSH