Production of Precursors for Anti-Alzheimer Drugs: Asymmetric Bioreduction in a Packed-Bed Bioreactor Using Immobilized D. Carota Cells

Abstract

(S)-1-Phenylethanol derivatives, which are the precursors of many pharmacological products, have also been used as anti-Alzheimer drugs. Bioreduction experiments were performed in a batch and packed-bed bioreactor. Then, the kinetics constants were determined by examining the reaction kinetics in the batch system with free and immobilized carrot cells. Also, the effective diffusion coefficient (De) of acetophenone in calcium alginate-immobilized carrot cells was investigated. Kinetics constants for free cells, which are intrinsic values, are reaction rate V-max - 0.052 mmol L-1 min(-1), and constants of the Michaelis-Menten K-M = 2.31 mmol L-1. Kinetics constants for immobilized cells, which are considered apparent values, are V-max,V- app = 0.0407 mmol L-1 min(-1), K-M,K- app = 3.0472 mmol L-1 for 2 mm bead diameter, and V-max,V- app = 0.0453 mmol L-1 min(-1), K-M,K- app = 4.9383 mmol L-1 for 3 mm bead diameter. Average value of effective diffusion coefficient of acetophenone in immobilized beads was determined as 1.97 x 10(-6) cm(2) s(-1). Using immobilized carrot cells in an up-flow packed-bed reactor, continuous production of (S)-1-phenylethanol through asymmetric bioreduction of acetophenone was performed. The effects of the residence time and concentrations of substrate were investigated at pH 7.6 and 33 degrees C. Enantiomerically pure (S)-1-phenylethanol (ee > 99%) was produced with 75% conversion at 4-hr residence time.