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

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• 作者：Matthew J. Byrne ; Nicholas R. Lees ; Li-Chen Han ; Marc W. van der Kamp ; Adrian J. Mulholland ; James E. M. Stach ; Christine L. Willis ; Paul R. Race
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：May 18, 2016
• 年：2016
• 卷：138
• 期：19
• 页码：6095-6098
• 全文大小：298K
• 年卷期：0
• ISSN：1520-5126

文摘

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.