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A Natural Diels‐Alder Biocatalyst Enables Efficient [4+2] Cycloaddition Under Harsh Reaction Conditions
Author(s) -
Marsh Carl O.,
Lees Nicholas R.,
Han LiChen,
Byrne Matthew J.,
Mbatha Sbusisiwe Z.,
Maschio Laurence,
PagdenRatcliffe Sebastian,
Duke Phillip W.,
Stach James E. M.,
Curnow Paul,
Willis Christine L.,
Race Paul R.
Publication year - 2019
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201901285
Subject(s) - biocatalysis , chemistry , cycloaddition , organic chemistry , chemical synthesis , organic synthesis , chemical stability , combinatorial chemistry , reaction mechanism , catalysis , biochemistry , in vitro
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 °C), and in the presence of organic solvents (MeOH, CH 3 CN and DMSO) and the chemical denaturant guanidinium hydrochloride, revealing that AbyU has potential widespread value as a biocatalyst.