title: Prediction of the pilot-scale recovery of a recombinant yeast enzyme using integrated models.
abstract: This article describes the rapid prediction of recovery process performance for a new recombinant enzyme product on the basis of a broad portfolio of computer models and highly targeted experimentation. A process model for the recombinant system was generated by linking unit operation models in an integrated fashion, with required parameter estimation and physical property determination accomplished using data from scale-down studies. This enabled the generic modeling framework established for processing of a natural enzyme from bakers' yeast to be applied. An experimental study of the same operations at the pilot scale showed that the process model gave a conservative prediction of recombinant enzyme recovery. The model successfully captured interactions leading to a low overall product yield and indicated the need for further study of precipitate breakage in the feed zone of a disc stack centrifuge in order to improve performance. The utility of scale-down units as an aid to fast model generation and the advantage of integrating computer modeling and scale-down studies to accelerate bioprocess development are highlighted.
authors.affiliation: The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
authors.forename: E G
authors.initials: EG
authors.lastname: Varga
authors.forename: N J
authors.initials: NJ
authors.lastname: Titchener-Hooker
authors.forename: P
authors.initials: P
authors.lastname: Dunnill
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D000645:Ammonium Sulfate / Q000737:chemistry; D002498:Centrifugation / Q000295:instrumentation; D011232:Chemical Precipitation; D004798:Enzymes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007218:Industrial Microbiology / Q000379:methods; D008962:Models, Theoretical; D010316:Particle Size; D010865:Pilot Projects; D011312:Pressure; D015202:Protein Engineering / Q000295:instrumentation / Q000379:methods*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism
chemical_list: D004798:Enzymes; D011994:Recombinant Proteins; D000426:Alcohol Dehydrogenase; D000645:Ammonium Sulfate