Affiliation:
1. Faculty of Pharmaceutical Sciences Hokkaido University Kita 12, Nishi 6, Kita-ku Sapporo 060-0812 Japan
Abstract
AbstractCupin/methionyl‐tRNA synthetase (MetRS)‐like didomain enzymes catalyze nitrogen‐nitrogen (N−N) bond formation between Nω‐hydroxylamines and amino acids to generate hydrazines, key biosynthetic intermediates of various natural products containing N−N bonds. While the combination of these two building blocks leads to the creation of diverse hydrazine products, the full extent of their structural diversity remains largely unknown. To explore this, we herein conducted phylogeny‐guided genome‐mining of related hydrazine biosynthetic pathways consisting of two enzymes: flavin‐dependent Nω‐hydroxylating monooxygenases (NMOs) that produce Nω‐hydroxylamine precursors and cupin/MetRS‐like enzymes that couple the Nω‐hydroxylamines with amino acids via N−N bonds. A phylogenetic analysis identified the largely unexplored sequence spaces of these enzyme families. The biochemical characterization of NMOs demonstrated their capabilities to produce various Nω‐hydroxylamines, including those previously not known as precursors of N−N bonds. Furthermore, the characterization of cupin/MetRS‐like enzymes identified five new hydrazine products with novel combinations of building blocks, including one containing non‐amino acid building blocks: 1,3‐diaminopropane and putrescine. This study substantially expanded the variety of N−N bond forming pathways mediated by cupin/MetRS‐like enzymes.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Japan Foundation for Applied Enzymology
Japan Agency for Medical Research and Development
Cited by
1 articles.
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