Recombinant protein production in Pichia pastoris under glyceraldehyde-3-phosphate dehydrogenase promoter: From carbon source metabolism to bioreactor operation parameters

ÇALIK P., Ata O., Gunes H., Massahi A., BOY E., KESKİN A., ...Daha Fazla

BIOCHEMICAL ENGINEERING JOURNAL, cilt.95, ss.20-36, 2015 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 95
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.bej.2014.12.003
  • Dergi Adı: BIOCHEMICAL ENGINEERING JOURNAL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.20-36
  • Anahtar Kelimeler: Bioreactors, Fed-batch culture, Bioprocess design, Fermentation, Pichia pastoris, GAP promoter, HIGH-LEVEL EXPRESSION, COLONY-STIMULATING FACTOR, HUMAN-ERYTHROPOIETIN PRODUCTION, L-METHIONINE BIOSYNTHESIS, GROWTH-HORMONE PRODUCTION, SINGLE-CHAIN ANTIBODY, HGM-CSF EXPRESSION, B SURFACE-ANTIGEN, CONSTITUTIVE EXPRESSION, METHYLOTROPHIC YEAST
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

The yeast Pichia (Komagataella) pastoris has become a potential host system for recombinant protein (r-protein) production. Several strong inducible and constitutive promoters have been identified in P. pastoris which make the host ideal in r-protein expressions. The constitutive promoter of the glyceraldehyde-3-phosphate dehydrogenase gene. P-GAp, is promising as its use offers the advantage of associating product quantity to growth which can be optimized by a well-designed feeding strategy so long as the product itself is not toxic to the host. In this article, carbon source metabolism and the central carbon pathways of P. pastoris are reviewed. After comparing P-GAp with the available promoters of P. pastoris, the bioreactor operation parameters and bioreactor operation strategies are analyzed for r-protein production under P-GAp by focusing on response of the cells, final product concentration, yield, and productivity. The overview of the subject reveals the requirement for in-depth information on the overall regulation of P. pastoris metabolism that can enable fine-tuning bioreactor operation parameters in relation with the physiology of the microorganism in order to develop new strategies for the enhanced r-protein production. (C) 2014 Elsevier B.V. All rights reserved.