TY - JOUR
T1 - A macrokinetic model-based comparative meta-analysis of recombinant protein production by Pichia pastoris under AOX1 promoter
AU - Barrigon, José Manuel
AU - Valero, Francisco
AU - Montesinos, José Luis
PY - 2015/6/1
Y1 - 2015/6/1
N2 - © 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.
AB - © 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.
KW - Bioprocess simulation
KW - Comparative analysis
KW - P AOX1
KW - Pichia pastoris
KW - Recombinant protein production
KW - Unstructured macrokinetic model
U2 - 10.1002/bit.25518
DO - 10.1002/bit.25518
M3 - Article
SN - 0006-3592
VL - 112
SP - 1132
EP - 1145
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
ER -