ArticleNature chemical biology2021
Co-occurrence of enzyme domains guides the discovery of an oxazolone synthetase.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Microbial unusual gene clusters without prominent core enzymes: natural products, biosynthesis and genome mining.The Journal of antibiotics · 2026Review
- ThiF-Like Enzyme Chemistry in Primary and Secondary Metabolism.Chembiochem : a European journal of chemical biology · 2025Review
- Sequence and taxonomic feature evaluation facilitated the discovery of alcohol oxidases.Synthetic and systems biotechnology · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Non-enzymatic reactions in biogenesis of fungal natural products.Journal of natural medicines · 2024Review
- Multi-omic analysis tools for microbial metabolites prediction.Briefings in bioinformatics · 2024Review
- Structure-Based Design of Small Imine Reductase Panels for Target Substrates.ACS catalysis · 2023Article
- Deciphering the biosynthesis of a novel lipid in Mycobacterium tuberculosis expands the known roles of the nitroreductase superfamily.The Journal of biological chemistry · 2023Article
- Bacterial natural product discovery by heterologous expression.Journal of industrial microbiology & biotechnology · 2023Review
- Integrated Metabolomic-Genomic Workflows Accelerate Microbial Natural Product Discovery.Analytical chemistry · 2022Review
- Strategies to access biosynthetic novelty in bacterial genomes for drug discovery.Nature reviews. Drug discovery · 2022Review
- Mining genomes to illuminate the specialized chemistry of life.Nature reviews. Genetics · 2021Review
- Phylogenetic analysis of the salinipostin γ-butyrolactone gene cluster uncovers new potential for bacterial signalling-molecule diversity.Microbial genomics · 2021Article
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3 authors at 1 institution in 1 country.
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Abstract
Multidomain enzymes orchestrate two or more catalytic activities to carry out metabolic transformations with increased control and speed. Here, we report the design and development of a genome-mining approach for targeted discovery of biochemical transformations through the analysis of co-occurring enzyme domains (CO-ED) in a single protein. CO-ED was designed to identify unannotated multifunctional enzymes for functional characterization and discovery based on the premise that linked enzyme domains have evolved to function collaboratively. Guided by CO-ED, we targeted an unannotated predicted ThiF-nitroreductase di-domain enzyme found in more than 50 proteobacteria. Through heterologous expression and biochemical reconstitution, we discovered a series of natural products containing the rare oxazolone heterocycle and characterized their biosynthesis. Notably, we identified the di-domain enzyme as an oxazolone synthetase, validating CO-ED-guided genome mining as a methodology with potential broad utility for both the discovery of unusual enzymatic transformations and the functional annotation of multidomain enzymes.
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