Publication
Article Metrics
Citations
Online attention
The Catalytic Mechanism of a Natural Diels–Alderase Revealed in Molecular Detail
Authors:
Matthew J.
Byrne
(University of Bristol)
,
Nicholas R.
Lees
(University of Bristol)
,
Li-chen
Han
(University of Bristol)
,
Marc W.
Van Der Kamp
(University of Bristol)
,
Adrian J.
Mulholland
(University of Bristol)
,
James E. M.
Stach
(Newcastle University)
,
Christine L.
Willis
(University of Bristol)
,
Paul R.
Race
(University of Bristol)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Journal Of The American Chemical Society
, VOL 138
, PAGES 6095 - 6098
State:
Published (Approved)
Published:
May 2016
Diamond Proposal Number(s):
8922
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.
Subject Areas:
Biology and Bio-materials,
Chemistry
Instruments:
I04-1-Macromolecular Crystallography (fixed wavelength)
,
I24-Microfocus Macromolecular Crystallography