Abstract
© 2015 Wiley Periodicals, Inc. 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.
Original language | English |
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Pages (from-to) | 1132-1145 |
Journal | Biotechnology and Bioengineering |
Volume | 112 |
DOIs | |
Publication status | Published - 1 Jun 2015 |
Keywords
- Bioprocess simulation
- Comparative analysis
- P AOX1
- Pichia pastoris
- Recombinant protein production
- Unstructured macrokinetic model