ArticleNature chemistry2019
Structural basis for stereoselective dehydration and hydrogen-bonding catalysis by the SAM-dependent pericyclase LepI.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed.
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- Using the Theozyme Model to Study the Dynamical Mechanism of the Post-Transition State Bifurcation Reaction by NgnD Enzyme.Molecules (Basel, Switzerland) · 2024Article
- Structural basis for substrate flexibility of the O-methyltransferase MpaG' involved in mycophenolic acid biosynthesis.Protein science : a publication of the Protein Society · 2024Article
- Characterization of a methyltransferase for iterative N-methylation at the leucinostatin termini in Purpureocillium lilacinum.Communications biology · 2024Article
- Structure of methyltransferase RedM that forms the dimethylpyrrolinium of the bisindole reductasporine.The Journal of biological chemistry · 2024Article
- Stereoselective Biocatalytic α-Deuteration of L-Amino Acids by a Pyridoxal 5'-Phosphate-Dependent Mannich Cyclase.Chembiochem : a European journal of chemical biology · 2023Article
- Review
- Normal and Aberrant Methyltransferase Activities Give Insights into the Final Steps of Dynemicin A Biosynthesis.Journal of the American Chemical Society · 2023Article
- EnzymaticJournal of the American Chemical Society · 2023Article
- Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining.Natural product reports · 2023Review
- Computational Prediction and Experimental Validation of a Bridged Cation Intermediate in Akanthomycin Biosynthesis.Journal of the American Chemical Society · 2022Article
- HarnessingJournal of natural products · 2022Review
- Anion-cation contrast of small molecule solvation in salt solutions.Physical chemistry chemical physics : PCCP · 2022Article
- Byproduct formation during the biosynthesis of spinosyn A and evidence for an enzymatic interplay to prevent its formation.Tetrahedron · 2022Article
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8 authors.
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Abstract
LepI is an S-adenosylmethionine (SAM)-dependent pericyclase that catalyses the formation of the 2-pyridone natural product leporin C. Biochemical characterization has shown that LepI can catalyse stereoselective dehydration to yield a reactive (E)-quinone methide that can undergo bifurcating intramolecular Diels-Alder (IMDA) and hetero-Diels-Alder (HDA) cyclizations from an ambimodal transition state, as well as a [3,3]-retro-Claisen rearrangement to recycle the IMDA product into leporin C. Here, we solve the X-ray crystal structures of SAM-bound LepI and in complex with a substrate analogue, the product leporin C, and a retro-Claisen reaction transition-state analogue to understand the structural basis for the multitude of reactions. Structural and mutational analysis reveals how nature evolves a classic methyltransferase active site into one that can serve as a dehydratase and a multifunctional pericyclase. Catalysis of both sets of reactions employs H133 and R295, two active-site residues that are not found in canonical methyltransferases. An alternative role of SAM, which is not found to be in direct contact with the substrate, is also proposed.
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