Payne T, et al. (2008) Modulation of Chaperone Gene Expression in Mutagenized Saccharomyces cerevisiae Strains Developed for Recombinant Human Albumin Production Results in Increased Production of Multiple Heterologous Proteins. Appl Environ Microbiol 74(24):7759-66
Abstract: The yeast S. cerevisiae has been successfully established as a commercially viable system for the production of recombinant proteins. Manipulation of chaperone gene expression has been utilised extensively to increase recombinant protein production from S. cerevisiae, focusing predominantly on the protein disulphide isomerise PDI1 and the hsp70 KAR2. Here we show that the expression of the genes SIL1, LHS1, JEM1 and SCJ1, all of which are involved in regulating the ATPase cycle of Kar2p, is increased in a proprietary yeast strain, developed by several rounds of random mutagenesis and screening for increased production of recombinant human albumin (rHA). To establish whether this expression contributes to the enhanced production phenotype, these genes were over-expressed both individually and in combination. The resultant strains showed significantly increased shake flask production levels of recombinant human albumin (rHA), granulocyte macrophage colony stimulating factor (GM-CSF) and recombinant human transferrin (rTf).
| Status: Published | Type: Journal Article | PubMed ID: 18931293 |
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