TY - JOUR
T1 - Rationalisation of the substrate concentration dependent diastereoselectivity of a Saccharomyces cerevisiae short-chain dehydrogenase
AU - Carlquist, Magnus
AU - Johanson, Ted
AU - Gorwa-Grauslund, Marie-Francoise
PY - 2007
Y1 - 2007
N2 - The diastereoselectivity of the carbonyl reduction of bicyclo[2.2.2]octane-2,6-dione, catalysed by the purified yeast cytosolic short-chain dehydrogenase Ymr226cp, was shown to be substrate concentration dependent. The changing selectivity was attributed to two distinct binding configurations of the substrate in the active site, each yielding a distinct hydroxy ketone diastereomer. By applying individual KM and Vmax values for each binding configuration, the concentration dependence could be modelled with Michaelis–Menten kinetics and the apparent KM and Vmax values for the generation of each diastereomer determined. This is to the best of our knowledge the first rationalisation of a substrate dependent stereoselectivity for a pro-chiral substrate with an isolated enzyme.
AB - The diastereoselectivity of the carbonyl reduction of bicyclo[2.2.2]octane-2,6-dione, catalysed by the purified yeast cytosolic short-chain dehydrogenase Ymr226cp, was shown to be substrate concentration dependent. The changing selectivity was attributed to two distinct binding configurations of the substrate in the active site, each yielding a distinct hydroxy ketone diastereomer. By applying individual KM and Vmax values for each binding configuration, the concentration dependence could be modelled with Michaelis–Menten kinetics and the apparent KM and Vmax values for the generation of each diastereomer determined. This is to the best of our knowledge the first rationalisation of a substrate dependent stereoselectivity for a pro-chiral substrate with an isolated enzyme.
U2 - 10.1016/j.tetasy.2007.10.020
DO - 10.1016/j.tetasy.2007.10.020
M3 - Article
SN - 0957-4166
VL - 18
SP - 2554
EP - 2556
JO - Tetrahedron: Asymmetry
JF - Tetrahedron: Asymmetry
IS - 21
ER -