In Vitro Reconstitution Reveals a Central Role for the N-Oxygenase PvfB in (Dihydro)pyrazine-N-oxide and Valdiazen Biosynthesis

被引：17

作者：

Morgan, Gina L. ^{[1
]}

Li, Bo ^{[1
]}

机构：

[1] Univ North Carolina Chapel Hill, Dept Chem, Chapel Hill, NC 27599 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2020年 / 59卷 / 48期

基金：

美国国家卫生研究院;

关键词：

biosynthesis; metalloenzymes; natural products; nitrogen heterocycles; protein modifications; NONRIBOSOMAL PEPTIDE SYNTHETASE; AURF; HYDROXYLASE; OXIDATION;

D O I：

10.1002/anie.202005554

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 alpha-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.

引用

页码：21387 / 21391

页数：5