Kinetic modeling of lipase catalyzed hydrolysis of ( R/ S)-1-methoxy-2-propyl-acetate as a model reaction for production of chiral secondary alcohols

Abstract

The Candida antarctica lipase B catalyzed kinetic resolution of ( R/ S)-1-methoxy-2-propyl-acetate was studied as a model system for the biocatalytic production of chiral secondary alcohols. For this purpose, a kinetic model is proposed involving both enantiomers of this reaction using model discrimination and parameter identification. Starting from a ping–pong bi–bi mechanism, a simplified model with sensitive parameters was derived for the R- and S-enantiomer, respectively. It was validated at pH 7.0, using time-course measurements at varying temperatures (30–60 °C) and initial substrate conditions (0.05–1.5 M). This model was then used for mechanistic interpretation of the kinetic resolution on a biochemical level. The effect of temperature on kinetic parameters and enantiomeric ratio was investigated and compared to findings from the field of molecular modeling to obtain a better understanding of the reaction system for process design. Values of 21.2 and 9.7 kJ mol −1 were determined for the enthalpic (Δ R– S Δ H ‡°) and the entropic (– T·Δ R– S Δ S ‡°) contribution of the difference in transition state energy of both enantiomers at 30 °C. High enantiomeric ratio's ( E of 47–110) especially at lower temperatures, in addition to enzyme activity at a wide pH range, indicate this biotransformation is a promising example for the industrial production of chiral secondary alcohols.