Carrier Protein Mediated Formation of the Dihydropyridazinone Ring in Actinopyridazinone Biosynthesis
Kuga Arima, Satoko Akiyama, Kazuo Shin‐ya, Kenichi Matsuda, Toshiyuki Wakimoto
Abstract
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.
Topics & Concepts
BiosynthesisStreptomycesChemistryRing (chemistry)In vitroProtein biosynthesisGeneCombinatorial chemistryBiochemistryStereochemistryComputational biologyBiologyGeneticsOrganic chemistryBacteriaMicrobial Natural Products and BiosynthesisClick Chemistry and ApplicationsChemical Synthesis and Analysis