Oxidation of deoxyaminosugars by a new flavin-dependent monooxygenase

Abstract

This research work aims to provide biochemical characterization of the enzyme(s) responsible for deoxyaminosugar oxidation in several glycosylated natural products. The enzyme homologues ORF36 and RubN8 from the everninomicn and the rubradirin biosynthetic pathways, respectively, were shown to catalyze amine to nitroso oxidation of the deoxyaminosugar TDP-L-epi-vancosamine. Catalysis was shown to proceed through two FAD/NADPH-dependent monooxygenation steps in which the aminosugar is first oxidized to the corresponding hydroxylamine, followed by a second N-oxygenation to form the nitrososugar. Intrestingly, DnmZ, a nitrososynthase homologue from Streptomyces peucetius, was shown to mediate a subsequent carbon-carbon bond cleavage of the formed β-hydroxy-nitrososugar. This retro-aldol activity represents a new and important addition to the functions known for flavin-dependent monooxygenases and expands our knowledge into late steps of baumycin biosynthesis.