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Metabolic engineering of recombinant protein secretion by Saccharomyces cerevisiae

  1. Jin Hou1,2,
  2. Keith E.J. Tyo1,3,
  3. Zihe Liu1,
  4. Dina Petranovic1,
  5. Jens Nielsen1,*

Article first published online: 17 MAY 2012

DOI: 10.1111/j.1567-1364.2012.00810.x

Issue

FEMS Yeast Research

FEMS Yeast Research

Volume 12, Issue 5, pages 491–510, August 2012

Additional Information

How to Cite

Hou, J., Tyo, K. E.J., Liu, Z., Petranovic, D. and Nielsen, J. (2012), Metabolic engineering of recombinant protein secretion by Saccharomyces cerevisiae. FEMS Yeast Research, 12: 491–510. doi: 10.1111/j.1567-1364.2012.00810.x

Author Information

  1. 1

    Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden

  2. 2

    State Key Laboratory of Microbial Technology, Shandong University, Jinan, China

  3. 3

    Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA

*Correspondence: Jens Nielsen, Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-412 96 Göteborg, Sweden. Tel.: +46 31 772 3804; fax: +46 31 772 3801;
e-mail: nielsenj@chalmers.se

Publication History

  1. Issue published online: 9 JUL 2012
  2. Article first published online: 17 MAY 2012
  3. Accepted manuscript online: 25 APR 2012 09:09AM EST
  4. Manuscript Accepted: 22 APR 2012
  5. Manuscript Revised: 19 APR 2012
  6. Manuscript Received: 16 JAN 2012

Funded by

  • NIH F32 Kirschstein NRSA fellowship
  • The Knut and Alice Wallenberg Foundation
  • EU Framework VII project SYSINBIO. Grant Number: 212766
  • European Research Council project INSYSBIO. Grant Number: 247013
  • Chalmers Foundation

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Keywords:

  • protein secretion;
  • systems biology;
  • yeast;
  • genetic engineering

Abstract

The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels and chemicals, and it is also provides a platform for the production of many heterologous proteins of medical or industrial interest. Therefore, many studies have focused on metabolic engineering S. cerevisiae to improve the recombinant protein production, and with the development of systems biology, it is interesting to see how this approach can be applied both to gain further insight into protein production and secretion and to further engineer the cell for improved production of valuable proteins. In this review, the protein post-translational modification such as folding, trafficking, and secretion, steps that are traditionally studied in isolation will here be described in the context of the whole system of protein secretion. Furthermore, examples of engineering secretion pathways, high-throughput screening and systems biology applications of studying protein production and secretion are also given to show how the protein production can be improved by different approaches. The objective of the review is to describe individual biological processes in the context of the larger, complex protein synthesis network.

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