ArticleNature chemical biology2015
An enzymatic [4+2] cyclization cascade creates the pentacyclic core of pyrroindomycins.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed.
- Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential.Chembiochem : a European journal of chemical biology · 2026Review
- Creating molecular complexity in the chemoenzymatic synthesis of chlorothricin analogues using tandem Diels-Alderases.Organic & biomolecular chemistry · 2026Article
- The Diels-Alder Reaction as a Key Step in Natural Product Synthesis.Progress in the chemistry of organic natural products · 2026Review
- Delineation of the complete reaction cycle of a natural Diels-Alderase.Chemical science · 2024Article
- Iron-sulphur protein catalysed [4+2] cycloadditions in natural product biosynthesis.Nature communications · 2024Article
- The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba.Nature communications · 2024Article
- Tandem intermolecular [4 + 2] cycloadditions are catalysed by glycosylated enzymes for natural product biosynthesis.Nature chemistry · 2023Article
- Interrogation of an Enzyme Library Reveals the Catalytic Plasticity of Naturally Evolved [4+2] Cyclases.Chembiochem : a European journal of chemical biology · 2023Article
- Biosynthesis of Polycyclic Natural Products from Conjugated Polyenes via Tandem Isomerization and Pericyclic Reactions.Journal of the American Chemical Society · 2023Article
- An NmrA-like enzyme-catalysed redox-mediated Diels-Alder cycloaddition with anti-selectivity.Nature chemistry · 2023Article
- AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis.Nature communications · 2022Article
- Discovery and characterization of a terpene biosynthetic pathway featuring a norbornene-forming Diels-Alderase.Nature communications · 2022Article
- Mechanism of the Stereoselective Catalysis of Diels-Alderase PyrE3 Involved in Pyrroindomycin Biosynthesis.Journal of the American Chemical Society · 2022Article
- Byproduct formation during the biosynthesis of spinosyn A and evidence for an enzymatic interplay to prevent its formation.Tetrahedron · 2022Article
- Molecular Basis for Two Stereoselective Diels-Alderases that Produce Decalin Skeletons*.Angewandte Chemie (International ed. in English) · 2021Article
- The crystal structure of AbsH3: A putative flavin adenine dinucleotide-dependent reductase in the abyssomicin biosynthesis pathway.Proteins · 2021Article
- Computational Investigation of the Mechanism of Diels-Alderase PyrI4.Journal of the American Chemical Society · 2020Article
- An enzymatic Alder-ene reaction.Nature · 2020Article
- Nonspecific Heme-Binding Cyclase, AbmU, Catalyzes [4 + 2] Cycloaddition during Neoabyssomicin Biosynthesis.ACS omega · 2020Article
- FAD-dependent enzyme-catalysed intermolecular [4+2] cycloaddition in natural product biosynthesis.Nature chemistry · 2020Article
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13 authors.
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Abstract
The [4+2] cycloaddition remains one of the most intriguing transformations in synthetic and natural products chemistry. In nature, however, there are remarkably few enzymes known to have this activity. We herein report an unprecedented enzymatic [4+2] cyclization cascade that has a central role in the biosynthesis of pyrroindomycins, which are pentacyclic spirotetramate natural products. Beginning with a linear intermediate that contains two pairs of 1,3-diene and alkene groups, the dedicated cyclases PyrE3 and PyrI4 act in tandem to catalyze the formation of two cyclohexene rings in the dialkyldecalin system and the tetramate spiro-conjugate of the molecules. The two cyclizations are completely enzyme dependent and proceed in a regio- and stereoselective manner to establish the enantiomerically pure pentacyclic core. Analysis of a related spirotetronate pathway confirms that homologs are functionally exchangeable, establishing the generality of these findings and explaining how nature creates diverse active molecules with similar rigid scaffolds.
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