Heterologous protein production using the Pichia pastoris expression system
Article first published online: 9 FEB 2005
Copyright © 2005 John Wiley & Sons, Ltd.
Volume 22, Issue 4, pages 249–270, March 2005
How to Cite
Macauley-Patrick, S., Fazenda, M. L., McNeil, B. and Harvey, L. M. (2005), Heterologous protein production using the Pichia pastoris expression system. Yeast, 22: 249–270. doi: 10.1002/yea.1208
- Issue published online: 9 FEB 2005
- Article first published online: 9 FEB 2005
- Manuscript Accepted: 30 NOV 2004
- Manuscript Received: 13 SEP 2004
- foreign protein production;
- heterologous expression;
- Pichia pastoris;
- post-translational modification;
- process optimization;
The Pichia pastoris expression system is being used successfully for the production of various recombinant heterologous proteins. Recent developments with respect to the Pichia expression system have had an impact on not only the expression levels that can be achieved, but also the bioactivity of various heterologous proteins. We review here some of these recent developments, as well as strategies for reducing proteolytic degradation of the expressed recombinant protein at cultivation, cellular and protein levels. The problems associated with post-translational modifications performed on recombinant proteins by P. pastoris are discussed, including the effects on bioactivity and function of these proteins, and some engineering strategies for minimizing unwanted glycosylations. We pay particular attention to the importance of optimizing the physicochemical environment for efficient and maximal recombinant protein production in bioreactors and the role of process control in optimizing protein production is reviewed. Finally, future aspects of the use of the P. pastoris expression system are discussed with regard to the production of complex membrane proteins, such as G protein-coupled receptors, and the industrial and clinical importance of these proteins. Copyright © 2005 John Wiley & Sons, Ltd.