A natural Diels‐Alder biocatalyst enables efficient [4 + 2] cycloaddition under harsh reaction conditions

DOI: 10.1002/cctc.201901285

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

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

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