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Genome-scale metabolic model of methylotrophic yeast Pichia pastoris and its use for in silico analysis of heterologous protein production.

Authors
  • Sohn, Seung Bum
  • Graf, Alexandra B
  • Kim, Tae Yong
  • Gasser, Brigitte
  • Maurer, Michael
  • Ferrer, Pau
  • Mattanovich, Diethard
  • Lee, Sang Yup
Type
Published Article
Journal
Biotechnology journal
Publication Date
Jul 01, 2010
Volume
5
Issue
7
Pages
705–715
Identifiers
DOI: 10.1002/biot.201000078
PMID: 20503221
Source
Medline
License
Unknown

Abstract

The methylotrophic yeast Pichia pastoris has gained much attention during the last decade as a platform for producing heterologous recombinant proteins of pharmaceutical importance, due to its ability to reproduce post-translational modification similar to higher eukaryotes. With the recent release of the full genome sequence for P. pastoris, in-depth study of its functions has become feasible. Here we present the first reconstruction of the genome-scale metabolic model of the eukaryote P. pastoris type strain DSMZ 70382, PpaMBEL1254, consisting of 1254 metabolic reactions and 1147 metabolites compartmentalized into eight different regions to represent organelles. Additionally, equations describing the production of two heterologous proteins, human serum albumin and human superoxide dismutase, were incorporated. The protein-producing model versions of PpaMBEL1254 were then analyzed to examine the impact on oxygen limitation on protein production.

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