ArticleNature2011
Enzyme-catalysed [4+2] cycloaddition is a key step in the biosynthesis of spinosyn A.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 313 citations in OpenAlex.
- Biosynthetic Diversity of Marine-DerivedMarine drugs · 2026Review
- Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential.Chembiochem : a European journal of chemical biology · 2026Review
- Multiscale machine learning molecular mechanics for mechanism and stereoselectivity of Diels-Alderase catalysis.Nature communications · 2026Article
- The Diels-Alder Reaction as a Key Step in Natural Product Synthesis.Progress in the chemistry of organic natural products · 2026Review
- Redefining Computational Enzymology with Multiscale Machine Learning/Molecular Mechanics: Catalytic Mechanism and Stereoselectivity in Diels-Alderases.Research square · 2025Article
- P450 Enzyme LyoI Performs Hydro-2,2'-Bifuran Oxidation in the Polyether Ionophore Lysocellin.Angewandte Chemie (International ed. in English) · 2025Article
- High-ThroughputACS central science · 2025Article
- An enzymatic dual-oxa Diels-Alder reaction constructs the oxygen-bridged tricyclic acetal unit of (-)-anthrabenzoxocinone.Nature chemistry · 2025Article
- Enhancement of spinosad production in Saccharopolyspora spinosa by overexpression of the complete 74-kb spinosyn gene cluster.Microbial cell factories · 2025Article
- Developing a robust genome editing tool based on an endogenous type I-B CRISPR-Cas system in Saccharopolyspora spinosa.Science China. Life sciences · 2025Article
- Interplay between Energy and Entropy Mediates Ambimodal Selectivity of Cycloadditions.Journal of chemical theory and computation · 2024Article
- Using the Theozyme Model to Study the Dynamical Mechanism of the Post-Transition State Bifurcation Reaction by NgnD Enzyme.Molecules (Basel, Switzerland) · 2024Article
- Recent advances in enzymatic carbon-carbon bond formation.RSC advances · 2024Review
- 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
- Valence-isomer selective cycloaddition reaction of cycloheptatrienes-norcaradienes.Nature communications · 2024Article
- Review
- A molecular electron density theory study of asymmetric Diels-Alder [4 + 2] reaction's mechanism of furan with three substituted alkynes (5-R substituted-3-(3-(phenylsulfonyl)-propioloyl)-oxazolidin-2-one).Journal of molecular modeling · 2023Article
- Tandem intermolecular [4 + 2] cycloadditions are catalysed by glycosylated enzymes for natural product biosynthesis.Nature chemistry · 2023Article
- Biosynthesis of Polycyclic Natural Products from Conjugated Polyenes via Tandem Isomerization and Pericyclic Reactions.Journal of the American Chemical Society · 2023Article
52 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
Funding
Abstract
The Diels-Alder reaction is a [4+2] cycloaddition reaction in which a cyclohexene ring is formed between a 1,3-diene and an electron-deficient alkene via a single pericyclic transition state. This reaction has been proposed as a key transformation in the biosynthesis of many cyclohexene-containing secondary metabolites. However, only four purified enzymes have thus far been implicated in biotransformations that are consistent with a Diels-Alder reaction, namely solanapyrone synthase, LovB, macrophomate synthase, and riboflavin synthase. Although the stereochemical outcomes of these reactions indicate that the product formation could be enzyme-guided in each case, these enzymes typically demonstrate more than one catalytic activity, leaving their specific influence on the cycloaddition step uncertain. In our studies of the biosynthesis of spinosyn A, a tetracyclic polyketide-derived insecticide from Saccharopolyspora spinosa, we identified a cyclase, SpnF, that catalyses a transannular [4+2] cycloaddition to form the cyclohexene ring in spinosyn A. Kinetic analysis demonstrates that SpnF specifically accelerates the ring formation reaction with an estimated 500-fold rate enhancement. A second enzyme, SpnL, was also identified as responsible for the final cross-bridging step that completes the tetracyclic core of spinosyn A in a manner consistent with a Rauhut-Currier reaction. This work is significant because SpnF represents the first example characterized in vitro of a stand-alone enzyme solely committed to the catalysis of a [4+2] cycloaddition reaction. In addition, the mode of formation of the complex perhydro-as-indacene moiety in spinosyn A is now fully established.
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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.