ArticleSynthetic and systems biotechnology2024
Nitric oxide synthase-guided genome mining identifies a cytochrome P450 enzyme for olefin nitration in bacterial specialized metabolism.
Article in Synthetic and systems biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 13 citations in OpenAlex.
- Unlocking a Nitrosuccinate Lyase for Decarboxylative Enzymatic Hydronitration.Angewandte Chemie (International ed. in English) · 2026Article
- Spirocyclic β-lactone secondary metabolites modulate spliceosome function.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genome mining and characterization of a heme-dependent enzyme catalyzing intermolecular Nitrogen-Nitrogen bond formation in hydrazinosuccinic acid biosynthesis.Synthetic and systems biotechnology · 2025Article
- Molecular Basis for Peptide Nitration by a Novel Cytochrome P450 Enzyme in RiPP Biosynthesis.ACS catalysis · 2025Article
- Iterative glycosylation on a single residue of a mature lasso peptide.Chemical science · 2025Article
- Biocatalytic Strategies for Nitration Reactions.JACS Au · 2025Review
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6 authors at 2 institutions in 1 country.
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Abstract
The biological signaling molecule nitric oxide (NO) has recently emerged as a metabolic precursor for the creation of microbial natural products with diversified structures and biological activities. Within the biosynthetic gene clusters (BGCs) of these compounds, genes associated with NO production pathways have been pinpointed. In this study, we employ a nitric oxide synthase (NOS)-guided genome mining strategy for the targeted discovery of NO-derived bacterial natural products and NO-utilizing biocatalysts. We show that a conserved NOS-containing BGC, distributed across several actinobacterial genomes, is responsible for the biosynthesis of lajollamycin, a unique nitro-tetraene-containing antibiotic whose biosynthetic mechanism remains elusive. Through a combination of in vivo and in vitro studies, we unveil the first cytochrome P450 enzyme capable of catalyzing olefin nitration in natural product biosynthesis. These results not only expand the current knowledge about biosynthetic nitration processes but also offer an efficient way for targeted identification of NO-utilizing metabolic pathways and novel nitrating biocatalysts.
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