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Genome mining and characterization of a heme-dependent enzyme catalyzing intermolecular Nitrogen-Nitrogen bond formation in hydrazinosuccinic acid biosynthesis.


ABSTRACT: Nitrogen-nitrogen (N-N) bond-forming enzymes are rare but play vital roles in both primary and secondary metabolism. Guided by a nitric oxide synthase (NOS)-based genome mining strategy, we report the discovery and characterization of a new heme-dependent enzyme system that catalyzes intermolecular N-N bond formation. Using both in vivo and in vitro reconstitution approaches, we demonstrated that a protein complex, comprising a heme enzyme and a 2[4Fe-4S] ferredoxin partner, mediates the coupling of the α-amine group of l-aspartate with inorganic nitrogen oxide species, such as nitrite or nitric oxide, to generate hydrazinosuccinic acid, a key biosynthetic precursor in several natural product pathways. Structural modeling and site-directed mutagenesis suggest a plausible catalytic mechanis

SUBMITTER: Shi J 

PROVIDER: S-EPMC12408219 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature