Affiliation:
1. Faculty of Pharmaceutical Sciences Hokkaido University Kita 12, Nishi 6, Kita-ku Sapporo 060-0812 Japan
2. National Institute of Advanced Industrial Science and Technology (AIST) Tokyo 135-0064 Japan
Abstract
AbstractHeterocycles 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.
Funder
Asahi Glass Foundation
Naito Foundation
Uehara Memorial Foundation
Sumitomo Foundation
Japan Agency for Medical Research and Development
ACT-X
Key Technology Research and Development Program of Shandong
Japan Society for the Promotion of Science
Subject
General Chemistry,Catalysis