ArticleNature chemical biology2019
Convergent biosynthetic transformations to a bacterial specialized metabolite.
Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed, 11 citations in OpenAlex.
- Biosynthesis of Terpenoid-Pyrrolobenzoxazine Hybrid Natural Product CJ-12662.Angewandte Chemie (International ed. in English) · 2022Article
- A shared mechanistic pathway for pyridoxal phosphate-dependent arginine oxidases.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Microbes produce specialized metabolites to thrive in their natural habitats. However, it is rare that a given specialized metabolite is biosynthesized via pathways with distinct intermediates and enzymes. Here, we show that the core assembly mechanism of the antibiotic indolmycin in marine gram-negative Pseudoalteromonas luteoviolacea is distinct from its counterpart in terrestrial gram-positive Streptomyces species, with a molecule that is a shunt product in the Streptomyces pathway employed as a biosynthetic substrate for a novel metal-independent N-demethylindolmycin synthase in the P. luteoviolacea pathway. To provide insight into this reaction, we solved the 1.5 Å resolution structure in complex with product and identified the active site residues. Guided by our biosynthetic insights, we then engineered the Streptomyces indolmycin producer for titer improvement. This study provides a paradigm for understanding how two unique routes to a microbial specialized metabolite can emerge from convergent biosynthetic transformations.
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