title: A multicomponent reaction-diffusion model of a heterogeneously distributed immobilized enzyme.
abstract: A physical model was derived for the synthesis of the antibiotic cephalexin with an industrial immobilized penicillin G acylase, called Assemblase. In reactions catalyzed by Assemblase, less product and more by-product are formed in comparison with a free-enzyme catalyzed reaction. The model incorporates reaction with a heterogeneous enzyme distribution, electrostatically coupled transport, and pH-dependent dissociation behavior of reactants and is used to obtain insight in the complex interplay between these individual processes leading to the suboptimal conversion. The model was successfully validated with synthesis experiments for conditions ranging from heavily diffusion limited to hardly diffusion limited, including substrate concentrations from 50 to 600 mM, temperatures between 273 and 303 K, and pH values between 6 and 9. During the conversion of the substrates into cephalexin, severe pH gradients inside the biocatalytic particle, which were previously measured by others, were predicted. Physical insight in such intraparticle process dynamics may give important clues for future biocatalyst design. The modular construction of the model may also facilitate its use for other bioconversions with other biocatalysts.
authors.affiliation: Department of Agrotechnology and Food Science, Food and Bioprocess Engineering Group, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands. Jeroen.vanRoon@wur.nl
authors.forename: J L
authors.initials: JL
authors.lastname: van Roon
authors.forename: M M H D
authors.initials: MM
authors.lastname: Arntz
authors.forename: A I
authors.initials: AI
authors.lastname: Kallenberg
authors.forename: M A
authors.initials: MA
authors.lastname: Paasman
authors.forename: J
authors.initials: J
authors.lastname: Tramper
authors.forename: C G P H
authors.initials: CG
authors.lastname: Schroën
authors.forename: H H
authors.initials: HH
authors.lastname: Beeftink
mesh_terms: D000465:Algorithms; D004058:Diffusion; D004800:Enzymes, Immobilized / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008962:Models, Theoretical; D015394:Molecular Structure; D010316:Particle Size; D010399:Penicillin Amidase / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D013696:Temperature
chemical_list: D004800:Enzymes, Immobilized; D010399:Penicillin Amidase