title: Stereoselective bioconversions in continuously operated fixed bed reactors: Modeling and process optimization.
abstract: The nonaqueous lipase-catalyzed kinetic resolution of racemic 2-methyl-1-pentanol in a continuously operated fixed bed reactor was theoretically and experimentally studied. A 2-dimensional mathematical model was developed to predict the performance of the heterogeneous enantioselective biotransformation and to optimize the productivity and effective stereoselectivity of the process by taking pore diffusion, solid(SINGLEBOND)liquid mass transfer, convection, and axial dispersion into account. Experimental investigations were conducted with lipase from Pseudomonas sp. immobilized by ionic binding in the pores of the anion exchange resin Duolite A 568. As determined in prior initial rate experiments, the specific activities of the immobilized lipase were maximal at a water activity of approximately a(w) = 0.67 and revealed a significant dependence on the amount of enzyme bound to the carrier material, with enantiomeric ratios slightly increasing with increasing water activities. Continuous resolution processes were carried out at a wide range of enzyme loadings. By controlled immobilization according to the theoretically evaluated optimal enzyme loading, the continuous racemic resolution could be optimized to obtain (R)-2-methyl-1-pentanol at high productivity and enantiopurity (ee > 95%). The steady-state characteristics of the system could be generally predicted by the model, despite the necessity to reevaluate the kinetic properties of the immobilized lipase to account for the complex non-aqueous microkinetics in a heterogeneous environment. Further model extension introducing competitive inhibition of free water in solutions as well as water diffusion and adsorption to the biocatalyst were useful in providing a more accurate description of the experimental results. (c) 1996 John Wiley & Sons, Inc.
authors.affiliation: University of Stuttgart, Institute for Biochemical Engineering, Allmandring 31, D-70569 Stuttgart, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Indlekofer
authors.forename: F
authors.initials: F
authors.lastname: Brotz
authors.forename: A
authors.initials: A
authors.lastname: Bauer
authors.forename: M
authors.initials: M
authors.lastname: Reuss