title: A macrokinetic model-based comparative meta-analysis of recombinant protein production by Pichia pastoris under AOX1 promoter.
abstract: An unstructured macrokinetic model for heterologous production of Rhizopus oryzae lipase (ROL) by a Pichia pastoris PAOX1 based system was developed. Mean specific rates and state variables for various fed-batch cultures, under methanol limited and non-limited conditions were used for modeling. The most representative kinetic functions (viz., Monod, Haldane, Pirt and Luedeking-Piret) were used for the specific rates of cell growth (µ), substrate consumption (qS ) and product formation (qP ). The performance of two different process models was assessed via simulation tests, using an overall validation procedure. The best model describes the cellular growth by a non-monotonic substrate function, substrate uptake via Pirt's equation and product formation through a Luedeking-Piret equation. A comparative meta-analysis of heterologous protein production of various target proteins by Pichia pastoris under AOX1 promoter was conducted and a general strategy for improving protein production from process kinetics was developed as a key to bioprocess optimization.
authors.affiliation: Departament d'Enginyeria Química, EE, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Barrigon
authors.forename: Francisco
authors.initials: F
authors.lastname: Valero
authors.forename: José Luis
authors.initials: JL
authors.lastname: Montesinos
mesh_terms: D042931:Aldehyde Oxidase / Q000235:genetics*; D003470:Culture Media / Q000737:chemistry; D015870:Gene Expression; D008049:Lipase / Q000096:biosynthesis* / Q000235:genetics*; D010843:Pichia / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012233:Rhizopus / Q000201:enzymology
chemical_list: D003470:Culture Media; D011994:Recombinant Proteins; D042931:Aldehyde Oxidase; D008049:Lipase
keywords: PAOX1; Pichia pastoris; bioprocess simulation; comparative analysis; recombinant protein production; unstructured macrokinetic model