Mapping the yeast host cell response to recombinant membrane protein production: relieving the biological bottlenecks

Mark P. Ashe, Roslyn M Bill

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding the structures and functions of membrane proteins is an active area of research within bioscience. Membrane proteins are key players in essential cellular processes such as the uptake of nutrients, the export of waste products, and the way in which cells communicate with their environment. It is therefore not surprising that membrane proteins are targeted by over half of all prescription drugs. Since most membrane proteins are not abundant in their native membranes, it is necessary to produce them in recombinant host cells to enable further structural and functional studies. Unfortunately, achieving the required yields of functional recombinant membrane proteins is still a bottleneck in contemporary bioscience. This has highlighted the need for defined and rational optimization strategies based upon experimental observation rather than relying on trial and error. We have published a transcriptome and subsequent genetic analysis that has identified genes implicated in high-yielding yeast cells. These results have highlighted a role for alterations to a cell's protein synthetic capacity in the production of high yields of recombinant membrane protein: paradoxically, reduced protein synthesis favors higher yields. These results highlight a potential bottleneck at the protein folding or translocation stage of protein production.
Original languageEnglish
Pages (from-to)707-714
Number of pages8
JournalBiotechnology Journal
Volume6
Issue number6
Early online date24 Mar 2011
DOIs
Publication statusPublished - Jun 2011

Bibliographical note

This is the pre-peer reviewed version of the following article Ashe, MP & Bill, RM 2011, 'Mapping the yeast host cell response to recombinant membrane protein production: relieving the biological bottlenecks', Biotechnology Journal, vol 6, no. 6, pp. 707-714 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/biot.201000333/abstract

Keywords

  • GTP-binding proteins
  • gene expression profiling
  • membrane proteins
  • biological models
  • nuclear proteins
  • protein biosynthesis
  • protein folding
  • protein transport
  • RNA-binding proteins
  • recombinant proteins
  • saccharomyces cerevisiae proteins
  • yeasts
  • stress
  • translation

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