Kinetic modeling of lipase catalyzed hydrolysis of (R/S)-1-methoxy-2-propyl-acetate as a model reaction for production of chiral secondary alcohols.
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 degrees 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 kJmol-1 were determined for the enthalpic (DeltaR-S DeltaH ++ degrees) and the entropic (-T x DeltaR-S DeltaS ++ degrees) contribution of the difference in transition state energy of both enantiomers at 30 degrees 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.
Berendsen
W R
WR
University of Stuttgart, Institute of Biochemical Engineering (IBVT), Allmandring 31, 70569 Stuttgart, Germany. WRBerendsen@gmx.net
Gendrot
G
G
Resnick
S
S
Reuss
M
M
D005656:Fungal Proteins; D006868:Hydrolysis; D008049:Lipase / Q000737:chemistry*; D008956:Models, Chemical; D011409:Propylene Glycols / Q000737:chemistry*; D013237:Stereoisomerism
D005656:Fungal Proteins; D011409:Propylene Glycols; D008049:Lipase; C431349:lipase B, Candida antarctica