Publication
Article Metrics
Citations
Online attention
A natural Diels‐Alder biocatalyst enables efficient [4 + 2] cycloaddition under harsh reaction conditions
Authors:
Carl
Marsh
(University of Bristol)
,
Nicholas
Lees
(University of Bristol)
,
Li-Chen
Han
(University of Bristol)
,
Matthew
Byrne
(University of Leeds)
,
Sbusisiwe
Mbatha
(University of Bristol)
,
Laurence
Maschio
(University of Bristol)
,
Sebastian
Pagden-Ratcliffe
(University of Bristol)
,
Phillip
Duke
(Defence Scientific and Technology Laboratory)
,
James
Stach
(Newcastle University)
,
Paul
Curnow
(University of Bristol)
,
Christine
Willis
(University of Bristol)
,
Paul
Race
(University of Bristol)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Chemcatchem
State:
Published (Approved)
Published:
August 2019
Diamond Proposal Number(s):
17212
Abstract: Carbon‐carbon bond formation is a fundamental transformation in both synthetic chemistry and biosynthesis. Enzymes catalyze such reactions with exquisite selectivity which often cannot be achieved using non‐biological methods but may suffer from an intolerance of high temperature and the presence of organic solvents limiting their applications. Here we report the thermodynamic and kinetic stability of the β‐barrel natural Diels‐Alderase AbyU, which catalyzes formation of the spirotetronate core of the antimicrobial natural product abyssomicin C, with creation of 3 new asymmetric centers. This enzyme is shown to catalyze [4 + 2] cycloadditions at elevated temperature (up to 65 oC), and in the presence of organic solvents (MeOH, CH3CN and DMSO) and the chemical denaturant guanidinium hydrochloride, revealing that AbyU has potential widespread value as a biocatalyst.
Journal Keywords: biocatalysis; Diels-Alderase; natural products; protein folding; cycloaddition
Diamond Keywords: Enzymes
Subject Areas:
Biology and Bio-materials,
Chemistry
Instruments:
I02-Macromolecular Crystallography
,
I03-Macromolecular Crystallography
,
I04-Macromolecular Crystallography
Added On:
27/09/2019 08:38
Discipline Tags:
Biochemistry
Catalysis
Chemistry
Structural biology
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)