The Catalytic Mechanism of a Natural Diels-Alderase Revealed in Molecular Detail

Matthew J. Byrne, Nick R Lees, Li Chen Han, Marc W. Van Der Kamp, Adrian J. Mulholland, James E M Stach, Christine L. Willis, Paul R. Race*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

75 Citations (Scopus)
471 Downloads (Pure)

Abstract

The Diels-Alder reaction, a [4 + 2] cycloaddition of a conjugated diene to a dienophile, is one of the most powerful reactions in synthetic chemistry. Biocatalysts capable of unlocking new and efficient Diels-Alder reactions would have major impact. Here we present a molecular-level description of the reaction mechanism of the spirotetronate cyclase AbyU, an enzyme shown here to be a bona fide natural Diels-Alderase. Using enzyme assays, X-ray crystal structures, and simulations of the reaction in the enzyme, we reveal how linear substrate chains are contorted within the AbyU active site to facilitate a transannular pericyclic reaction. This study provides compelling evidence for the existence of a natural enzyme evolved to catalyze a Diels-Alder reaction and shows how catalysis is achieved.

Original languageEnglish
Pages (from-to)6095-6098
Number of pages4
JournalJournal of the American Chemical Society
Volume138
Issue number19
Early online date6 May 2016
DOIs
Publication statusPublished - 18 May 2016

Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio
  • BCS and TECS CDTs

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