A structured kinetic model for recombinant protein production by Mut(+) strain of Pichia pastoris

Celik E., ÇALIK P., Oliver S. G.

CHEMICAL ENGINEERING SCIENCE, cilt.64, sa.23, ss.5028-5035, 2009 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 64 Sayı: 23
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1016/j.ces.2009.08.009
  • Dergi Adı: CHEMICAL ENGINEERING SCIENCE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.5028-5035
  • Anahtar Kelimeler: Mathematical modelling, Parameter identification, Biochemical engineering, Bioprocessing, Fed-batch fermentation, Pichia pastoris, ALCOHOL OXIDASE, MIXED-FEEDS, FERMENTATION, METHANOL, GLYCEROL, GROWTH, BATCH, AVIDIN
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

A structured kinetic biochemical model for Pichia pastoris growth and recombinant protein production, able to predict r-protein production and optimize the feeding strategy is reported. Pichia pastoris was divided into three compartments, the recombinant product human erythropoietin (rHuEPO) was considered in one compartment, alcohol oxidase and extracellular protease enzymes were assembled in the enzymatic compartment, and rest of the cell components (including intracellular proteases) were gathered in the cellular compartment. After parameter identification by the simplex method, sensitivity analysis was carried out to confirm that the global optimum values were reached for the parameters of the model. The model successfully simulated the dynamic changes and the resulting rHuEPO production caused by variations in methanol feeding rate, even in the lag and the stationary phases. The model successfully predicted the optimal feeding strategies and has great potential for use in process simulation and control of glycosylated recombinant protein production by Pichia pastoris cells. (C) 2009 Elsevier Ltd. All rights reserved.