title: Substrate-Determined Diastereoselectivity in an Enzymatic Carboligation.
abstract: Thiamine diphosphate-dependent enzymes catalyze the formation of C-C bonds, thereby generating chiral secondary or tertiary alcohols. By the use of vibrational circular dichroism (VCD) spectroscopy we studied the stereoselectivity of carboligations catalyzed by YerE, a carbohydrate-modifying enzyme from Yersinia pseudotuberculosis. Conversion of the non-physiological substrate (R)-3-methylcyclohexanone led to an R,R-configured tertiary alcohol (diastereomeric ratio (dr) >99:1), whereas the corresponding reaction with the S enantiomer gave the S,S-configured product (dr>99:1). This suggests that YerE-catalyzed carboligations can undergo either an R- or an S-specific pathway. We show that, in this case, the high stereoselectivity of the YerE-catalyzed reaction depends on the substrate's preference to acquire a low-energy conformation.
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lehwald
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Fuchs
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, NY, 13244, USA.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Nafie
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104, Freiburg, Germany. steffen.luedeke@pharmazie.uni-freiburg.de.
authors.forename: Steffen
authors.identifier: 0000-0003-1498-5552
authors.initials: S
authors.lastname: Lüdeke
mesh_terms: D019755:Carbon-Carbon Lyases / Q000737:chemistry*; D002942:Circular Dichroism; D003511:Cyclohexanols / Q000737:chemistry; D003512:Cyclohexanones / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D015011:Yersinia pseudotuberculosis / Q000201:enzymology
chemical_list: D003511:Cyclohexanols; D003512:Cyclohexanones; D019755:Carbon-Carbon Lyases
keywords: chemoselectivity; conformation analysis; diastereoselectivity; enzyme catalysis; tertiary alcohols; vibrational circular dichroism