ArticleNature chemistry2020
FAD-dependent enzyme-catalysed intermolecular [4+2] cycloaddition in natural product biosynthesis.
Article in Nature chemistry, 2020. 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, 157 citations in OpenAlex.
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- MAPLE: a machine-learning force-field-native platform for automated reaction modeling and enzyme design.Chemical science · 2026Article
- Characterization of the biosynthetic enzymes of theScience advances · 2026Article
- A Computational Investigation of Four Sesquiterpene [4+2] Trimers, Inubritantrimers A-D, and Their Synthetic Intermediates Isolated fromMolecules (Basel, Switzerland) · 2026Article
- Multiscale machine learning molecular mechanics for mechanism and stereoselectivity of Diels-Alderase catalysis.Nature communications · 2026Article
- Redefining Computational Enzymology with Multiscale Machine Learning/Molecular Mechanics: Catalytic Mechanism and Stereoselectivity in Diels-Alderases.Research square · 2025Article
- Structural and biochemical basis for cannabinoid cyclase activity in marine bacterial flavoenzymes.bioRxiv : the preprint server for biology · 2025Article
- Chalasoergodimers A-E, heterodimers with multiple polymerization modes from a marine-derived Chaetomium sp. fungus.Natural products and bioprospecting · 2025Article
- Aspartic acid residues in BBE-like enzymes fromProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dihydroartemisinic acid dehydrogenase-mediated alternative route for artemisinin biosynthesis.Nature communications · 2025Article
- Advances in synthesizing plant-derived isoflavones and their precursors with multiple pharmacological activities using engineered yeasts.Microbial cell factories · 2025Review
- Article
- Understanding metabolic diversification in plants: branchpoints in the evolution of specialized metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Biosynthetic Strategies of Berberine Bridge Enzyme-like Flavoprotein Oxidases toward Structural Diversification in Natural Product Biosynthesis.Biochemistry · 2024Review
- Delineation of the complete reaction cycle of a natural Diels-Alderase.Chemical science · 2024Article
- Discovery of a Potent Antiosteoporotic Drug Molecular Scaffold Derived fromACS central science · 2024Article
- The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba.Nature communications · 2024Article
- Chemoproteomics, A Broad Avenue to Target Deconvolution.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations.Beilstein journal of organic chemistry · 2024Review
- Chemoproteomics approach to elucidating biosynthetic pathway of plant natural products.Frontiers in plant science · 2024Article
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Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Diels-Alder reaction is one of the most powerful and widely used methods in synthetic chemistry for the stereospecific construction of carbon-carbon bonds. Despite the importance of Diels-Alder reactions in the biosynthesis of numerous secondary metabolites, no naturally occurring stand-alone Diels-Alderase has been demonstrated to catalyse intermolecular Diels-Alder transformations. Here we report a flavin adenine dinucleotide-dependent enzyme, Morus alba Diels-Alderase (MaDA), from Morus cell cultures, that catalyses an intermolecular [4+2] cycloaddition to produce the natural isoprenylated flavonoid chalcomoracin with a high efficiency and enantioselectivity. Density functional theory calculations and preliminary measurements of the kinetic isotope effects establish a concerted but asynchronous pericyclic pathway. Structure-guided mutagenesis and docking studies demonstrate the interactions of MaDA with the diene and dienophile to catalyse the [4+2] cycloaddition. MaDA exhibits a substrate promiscuity towards both dienes and dienophiles, which enables the expedient syntheses of structurally diverse natural products. We also report a biosynthetic intermediate probe (BIP)-based target identification strategy used to discover MaDA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.