An efficient and regioselective biocatalytic synthesis of aromatic N-oxides by using a soluble di-iron monooxygenase PmlABCDEF produced in the Pseudomonas species.

Abstract

SummaryHere, we present an improved whole‐cell biocatalysis system for the synthesis of heteroaromatic N‐oxides based on the production of a soluble di‐iron monooxygenase PmlABCDEF in Pseudomonas sp. MIL9 and Pseudomonas putida KT2440. The presented biocatalysis system performs under environmentally benign conditions, features a straightforward and inexpensive procedure and possesses a high substrate conversion and product yield. The capacity of gram‐scale production was reached in the simple shake‐flask cultivation. The template substrates (pyridine, pyrazine, 2‐aminopyrimidine) have been converted into pyridine‐1‐oxide, pyrazine‐1‐oxide and 2‐aminopyrimidine‐1‐oxide in product titres of 18.0, 19.1 and 18.3 g l‐1, respectively. To our knowledge, this is the highest reported productivity of aromatic N‐oxides using biocatalysis methods. Moreover, comparing to the chemical method of aromatic N‐oxides synthesis based on meta‐chloroperoxybenzoic acid, the developed approach is applicable for a regioselective oxidation that is an additional advantageous option in the preparation of the anticipated N‐oxides.