Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Dr James StachORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Chemical Society, 2016.

For re-use rights please refer to the publisher's terms and conditions.


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.

Publication metadata

Author(s): Byrne MJ, Lees NR, Han LC, van der Kamp MW, Mulholland AJ, Stach JEM, Willis CL, Race PR

Publication type: Article

Publication status: Published

Journal: Journal of the American Chemical Society

Year: 2016

Volume: 138

Issue: 19

Pages: 6095-6098

Print publication date: 18/05/2016

Online publication date: 03/05/2016

Acceptance date: 02/04/2016

Date deposited: 23/09/2016

ISSN (print): 0002-7863

ISSN (electronic): 1520-5126

Publisher: American Chemical Society


DOI: 10.1021/jacs.6b00232


Altmetrics provided by Altmetric


Funder referenceFunder name
BB/L01386X/1EPSRC through the BrisSynBio Synthetic Biology Research Centre
BB/M026280/1BBSRC David Phillips Fellowship