title: Enhancing the enantioselectivity of an epoxide hydrolase by directed evolution.
abstract: [reaction: see text] The epoxide hydrolase (EH) from Aspergillus niger, which shows a selectivity factor of only E = 4.6 in the hydrolytic kinetic resolution of glycidyl phenyl ether, has been subjected to directed evolution for the purpose of enhancing enantioselectivity. After only one round of error-prone polymerase chain reaction (epPCR), enantioselectivity was more than doubled (E = 10.8). The improved mutant enzyme contains three amino acid exchanges, two of which are spatially far from the catalytically active center.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim/Ruhr, Germany, Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, 97078 Würzburg, Germany. reetz@mpi-muelheim.mpg.de
authors.forename: Manfred T
authors.initials: MT
authors.lastname: Reetz
authors.forename: Claudia
authors.initials: C
authors.lastname: Torre
authors.forename: Andreas
authors.initials: A
authors.lastname: Eipper
authors.forename: Renate
authors.initials: R
authors.lastname: Lohmer
authors.forename: Marcus
authors.initials: M
authors.lastname: Hermes
authors.forename: Birgit
authors.initials: B
authors.lastname: Brunner
authors.forename: Andrea
authors.initials: A
authors.lastname: Maichele
authors.forename: Marco
authors.initials: M
authors.lastname: Bocola
authors.forename: Michael
authors.initials: M
authors.lastname: Arand
authors.forename: Annette
authors.initials: A
authors.lastname: Cronin
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Genzel
authors.forename: Alain
authors.initials: A
authors.lastname: Archelas
authors.forename: Roland
authors.initials: R
authors.lastname: Furstoss
mesh_terms: D001234:Aspergillus niger / Q000201:enzymology; D002384:Catalysis; D018360:Crystallography, X-Ray; D019020:Directed Molecular Evolution; D004851:Epoxide Hydrolases / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000737:chemistry; D011487:Protein Conformation; D013237:Stereoisomerism
chemical_list: D010647:Phenyl Ethers; C016050:phenylglycidyl ether; D004851:Epoxide Hydrolases