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In Vitro Reconstitution Reveals a Central Role for the N‐Oxygenase PvfB in (Dihydro)pyrazine‐ N ‐oxide and Valdiazen Biosynthesis
Author(s) -
Morgan Gina L.,
Li Bo
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202005554
Subject(s) - biosynthesis , chemistry , hydroxylamine , oxygenase , valine , pyrazine , operon , stereochemistry , natural product , reactivity (psychology) , biochemistry , enzyme , amino acid , gene , escherichia coli , medicine , alternative medicine , pathology
The Pseudomonas virulence factor (pvf) operon is essential for the biosynthesis of two very different natural product scaffolds: the (dihydro)pyrazine‐N‐oxides and the diazeniumdiolate, valdiazen. PvfB is a member of the non‐heme diiron N‐oxygenase enzyme family that commonly convert anilines to their nitroaromatic counterparts. In contrast, we show that PvfB catalyzes N‐oxygenation of the α‐amine of valine, first to the hydroxylamine and then the nitroso, while linked to the carrier protein of PvfC. PvfB modification of PvfC‐tethered valine was observed directly by protein NMR spectroscopy, establishing the intermediacy of the hydroxylamine. This work reveals a central role for PvfB in the biosynthesis of (dihydro)pyrazine‐N‐oxides and valdiazen.