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Publication - Dr Paul Race

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

    Citation

    Byrne, MJ, Lees, NR, Han, LC, Van Der Kamp, MW, Mulholland, AJ, Stach, JEM, Willis, CL & Race, PR, 2016, ‘The Catalytic Mechanism of a Natural Diels-Alderase Revealed in Molecular Detail’. Journal of the American Chemical Society, vol 138., pp. 6095-6098

    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.

    Full details in the University publications repository