Laboratory-Evolved Enzymes Provide Snapshots of the Development of Enantioconvergence in Enzyme-Catalyzed Epoxide Hydrolysis
Janfalk Carlsson, Åsa ; Bauer, Paul ; Dobritzsch, Doreen ; Nilsson, Mikael ; Kamerlin, S C Lynn LU
and Widersten, Mikael
(2016)
In ChemBioChem
17(18).
p.7-1693
- Abstract
Engineered enzyme variants of potato epoxide hydrolase (StEH1) display varying degrees of enrichment of (2R)-3-phenylpropane-1,2-diol from racemic benzyloxirane. Curiously, the observed increase in the enantiomeric excess of the (R)-diol is not only a consequence of changes in enantioselectivity for the preferred epoxide enantiomer, but also to changes in the regioselectivity of the epoxide ring opening of (S)-benzyloxirane. In order to probe the structural origin of these differences in substrate selectivity and catalytic regiopreference, we solved the crystal structures for the evolved StEH1 variants. We used these structures as a starting point for molecular docking studies of the epoxide enantiomers into the respective active sites.... (More)
Engineered enzyme variants of potato epoxide hydrolase (StEH1) display varying degrees of enrichment of (2R)-3-phenylpropane-1,2-diol from racemic benzyloxirane. Curiously, the observed increase in the enantiomeric excess of the (R)-diol is not only a consequence of changes in enantioselectivity for the preferred epoxide enantiomer, but also to changes in the regioselectivity of the epoxide ring opening of (S)-benzyloxirane. In order to probe the structural origin of these differences in substrate selectivity and catalytic regiopreference, we solved the crystal structures for the evolved StEH1 variants. We used these structures as a starting point for molecular docking studies of the epoxide enantiomers into the respective active sites. Interestingly, despite the simplicity of our docking analysis, the apparent preferred binding modes appear to rationalize the experimentally determined regioselectivities. The analysis also identifies an active site residue (F33) as a potentially important interaction partner, a role that could explain the high conservation of this residue during evolution. Overall, our experimental, structural, and computational studies provide snapshots into the evolution of enantioconvergence in StEH1-catalyzed epoxide hydrolysis.
(Less)
- author
- Janfalk Carlsson, Åsa
; Bauer, Paul
; Dobritzsch, Doreen
; Nilsson, Mikael
; Kamerlin, S C Lynn
LU
and Widersten, Mikael
- publishing date
- 2016-09-15
- type
- Contribution to journal
- publication status
- published
- keywords
- Biocatalysis, Directed Molecular Evolution, Epoxide Hydrolases/metabolism, Epoxy Compounds/chemistry, Hydrolysis, Molecular Docking Simulation, Molecular Structure, Solanum tuberosum/enzymology
- in
- ChemBioChem
- volume
- 17
- issue
- 18
- pages
- 5 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:84980008659
- pmid:27383542
- ISSN
- 1439-4227
- DOI
- 10.1002/cbic.201600330
- language
- English
- LU publication?
- no
- additional info
- © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
- id
- e81f816f-8711-4363-9c15-c0c44a299ff0
- date added to LUP
- 2025-01-11 21:30:08
- date last changed
- 2025-01-21 03:19:56
@article{e81f816f-8711-4363-9c15-c0c44a299ff0,
abstract = {{<p>Engineered enzyme variants of potato epoxide hydrolase (StEH1) display varying degrees of enrichment of (2R)-3-phenylpropane-1,2-diol from racemic benzyloxirane. Curiously, the observed increase in the enantiomeric excess of the (R)-diol is not only a consequence of changes in enantioselectivity for the preferred epoxide enantiomer, but also to changes in the regioselectivity of the epoxide ring opening of (S)-benzyloxirane. In order to probe the structural origin of these differences in substrate selectivity and catalytic regiopreference, we solved the crystal structures for the evolved StEH1 variants. We used these structures as a starting point for molecular docking studies of the epoxide enantiomers into the respective active sites. Interestingly, despite the simplicity of our docking analysis, the apparent preferred binding modes appear to rationalize the experimentally determined regioselectivities. The analysis also identifies an active site residue (F33) as a potentially important interaction partner, a role that could explain the high conservation of this residue during evolution. Overall, our experimental, structural, and computational studies provide snapshots into the evolution of enantioconvergence in StEH1-catalyzed epoxide hydrolysis.</p>}},
author = {{Janfalk Carlsson, Åsa and Bauer, Paul and Dobritzsch, Doreen and Nilsson, Mikael and Kamerlin, S C Lynn and Widersten, Mikael}},
issn = {{1439-4227}},
keywords = {{Biocatalysis; Directed Molecular Evolution; Epoxide Hydrolases/metabolism; Epoxy Compounds/chemistry; Hydrolysis; Molecular Docking Simulation; Molecular Structure; Solanum tuberosum/enzymology}},
language = {{eng}},
month = {{09}},
number = {{18}},
pages = {{7--1693}},
publisher = {{John Wiley & Sons Inc.}},
series = {{ChemBioChem}},
title = {{Laboratory-Evolved Enzymes Provide Snapshots of the Development of Enantioconvergence in Enzyme-Catalyzed Epoxide Hydrolysis}},
url = {{http://dx.doi.org/10.1002/cbic.201600330}},
doi = {{10.1002/cbic.201600330}},
volume = {{17}},
year = {{2016}},
}