Research Article

You have free access to this content

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

  1. Seung Bum Sohn1,2,
  2. Alexandra B. Graf3,4,
  3. Tae Yong Kim1,2,
  4. Brigitte Gasser3,
  5. Michael Maurer4,
  6. Pau Ferrer5,
  7. Diethard Mattanovich Professor3,
  8. Sang Yup Lee Professor1,2,6,*

Article first published online: 25 MAY 2010

DOI: 10.1002/biot.201000078

Issue

Biotechnology Journal

Biotechnology Journal

Special Issue: Systems Biology for Biotech Applications

Volume 5, Issue 7, pages 705–715, July 2010

Additional Information

How to Cite

Sohn, S. B., Graf, A. B., Kim, T. Y., Gasser, B., Maurer, M., Ferrer, P., Mattanovich, D. and Lee, S. Y. (2010), Genome-scale metabolic model of methylotrophic yeast Pichia pastoris and its use for in silico analysis of heterologous protein production. Biotechnology Journal, 5: 705–715. doi: 10.1002/biot.201000078

Author Information

  1. 1

    Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon, Republic of Korea

  2. 2

    Bioinformatics Research Center, KAIST, Daejeon, Republic of Korea

  3. 3

    Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria

  4. 4

    School of Bioengineering, University of Applied Sciences FH-Campus Wien, Vienna, Austria

  5. 5

    Department d'Enginyeria Química, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Bellaterra, Spain

  6. 6

    Department of Bio and Brain Engineering and Bioinformatics Research Center, KAIST, Daejeon, Republic of Korea

*Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon 305-701, Republic of Korea, Fax: +82423503910

Publication History

  1. Issue published online: 14 JUL 2010
  2. Article first published online: 25 MAY 2010
  3. Manuscript Accepted: 18 MAY 2010
  4. Manuscript Revised: 13 MAY 2010
  5. Manuscript Received: 3 MAY 2010

Funded by

  • Korean Systems Biology Research Project of the Ministry of Education, Science and Technology through the National Research Foundation of Korea
  • Austrian Science Fund
  • Austrian Research Promotion Agency

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (646K)

Keywords:

  • Genome-scale metabolic model;
  • Heterologous protein production;
  • HSA;
  • hSOD;
  • Pichia pastoris

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.

Get PDF (646K)