Effect of mass transfer limitations on the enzymatic kinetic resolution of epoxides in a two-liquid-phase system

Optically active epoxides can be obtained by kinetic resolution of racemic mixtures using enantiose- lective epoxide hydrolases. To increase the productivity of the conversion of sparingly aqueous soluble epoxides, we investigated the use of a two-phase aqueous/organic system. A kinetic model which takes into account inter- phase mass transfer, enzymatic reaction, and enzyme inactivation was developed to describe epoxide conver- sion in the system by the epoxide hydrolase from Agro- bacterium radiobacter. A Lewis cell was used to deter- mine model parameters and results from resolutions car- ried out in the Lewis cell were compared to model predictions to validate the model. It was found that n- octane is a biocompatible immiscible solvent suitable for use as the organic phase. Good agreement between the model predictions and experimental data was found when the enzyme inactivation rate was fitted. Simula- tions showed that mass transfer limitations have to be avoided in order to maximize the yield of enantiomeri- cally pure epoxide. Resolution of a 39 g/L solution of racemic styrene oxide in octane was successfully carried out in an emulsion batch reactor to obtain (S)-styrene oxide in high enantiomeric excess (>95% e.e.) with a yield of 30%. © 2001 John Wiley & Sons, Inc. Biotechnol Bio- eng 73: 44-54, 2001.