Integrating metabolic modeling and population heterogeneity analysis into optimizing recombinant protein production by Komagataella (Pichia) pastoris

Chrispian W. Theron, JULIO ANDRES BERRIOS ARAYA, Frank Delvigne, Patrick Fickers

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

The methylotrophic yeast Komagataella (Pichia) pastoris has become one of the most utilized cell factories for the production of recombinant proteins over the last three decades. This success story is linked to its specific physiological traits, i.e., the ability to grow at high cell density in inexpensive culture medium and to secrete proteins at high yield. Exploiting methanol metabolism is at the core of most P. pastoris-based processes but comes with its own challenges. Co-feeding cultures with glycerol/sorbitol and methanol is a promising approach, which can benefit from improved understanding and prediction of metabolic response. The development of profitable processes relies on the construction and selection of efficient producing strains from less efficient ones but also depends on the ability to master the bioreactor process itself. More specifically, how a bioreactor processes could be monitored and controlled to obtain high yield of production. In this review, new perspectives are detailed regarding a multi-faceted approach to recombinant protein production processes by P. pastoris; including gaining improved understanding of the metabolic pathways involved, accounting for variations in transcriptional and translational efficiency at the single cell level and efficient monitoring and control of methanol levels at the bioreactor level.

Original languageEnglish
Pages (from-to)63-80
Number of pages18
JournalApplied Microbiology and Biotechnology
Volume102
Issue number1
DOIs
StatePublished - 1 Jan 2018

Keywords

  • Methanol regulation
  • Modeling
  • pAOX1
  • Phenotypic heterogeneity
  • Pichia pastoris
  • Sorbitol co-feeding

Fingerprint Dive into the research topics of 'Integrating metabolic modeling and population heterogeneity analysis into optimizing recombinant protein production by Komagataella (Pichia) pastoris'. Together they form a unique fingerprint.

Cite this