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      A macrokinetic model-based comparative meta-analysis of recombinant protein production by Pichia pastoris under AOX1 promoter.

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          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.

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          Author and article information

          Journal
          Biotechnol. Bioeng.
          Biotechnology and bioengineering
          Wiley-Blackwell
          1097-0290
          0006-3592
          Jun 2015
          : 112
          : 6
          Affiliations
          [1 ] Departament d'Enginyeria Química, EE, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain.
          Article
          10.1002/bit.25518
          25546846
          5d38d207-5597-4a82-a3b5-fdd37f5ffc1e
          History

          PAOX1,Pichia pastoris,bioprocess simulation,comparative analysis,recombinant protein production,unstructured macrokinetic model

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