ArticleNature communications2024
The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- 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
- Multiscale machine learning molecular mechanics for mechanism and stereoselectivity of Diels-Alderase catalysis.Nature communications · 2026Article
- Discover the maze-like network for glabridin biosynthesis.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
- Aspartic acid residues in BBE-like enzymes fromProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Biomimetic Total Synthesis and Paired Omics Identify an Intermolecular Diels-Alder Reaction as the Key Step in Lugdunomycin Biosynthesis.Journal of the American Chemical Society · 2025Article
- Evolutionary insights into the stereoselectivity of imine reductases based on ancestral sequence reconstruction.Nature communications · 2024Article
- Biosynthetic Strategies of Berberine Bridge Enzyme-like Flavoprotein Oxidases toward Structural Diversification in Natural Product Biosynthesis.Biochemistry · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biosynthetic enzymes evolutionarily gain novel functions, thereby expanding the structural diversity of natural products to the benefit of host organisms. Diels-Alderases (DAs), functionally unique enzymes catalysing [4 + 2] cycloaddition reactions, have received considerable research interest. However, their evolutionary mechanisms remain obscure. Here, we investigate the evolutionary origins of the intermolecular DAs in the biosynthesis of Moraceae plant-derived Diels-Alder-type secondary metabolites. Our findings suggest that these DAs have evolved from an ancestor functioning as a flavin adenine dinucleotide (FAD)-dependent oxidocyclase (OC), which catalyses the oxidative cyclisation reactions of isoprenoid-substituted phenolic compounds. Through crystal structure determination, computational calculations, and site-directed mutagenesis experiments, we identified several critical substitutions, including S348L, A357L, D389E and H418R that alter the substrate-binding mode and enable the OCs to gain intermolecular DA activity during evolution. This work provides mechanistic insights into the evolutionary rationale of DAs and paves the way for mining and engineering new DAs from other protein families.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.