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Background  The yeast  Saccharomyces cerevisiae  provides intriguing possibilities for synthetic biology and bioprocess applications, but its use is still constrained by cellular characteristics that limit the product yields. Considering the production of advanced biopharmaceuticals, a major hindrance lies in the yeast endoplasmic reticulum (ER), as it is not equipped for efficient and large scale folding of complex proteins, such as human antibodies.    Results  Following the example of professional secretory cells, we show that inducing an ER expansion in yeast by deleting the lipid-regulator gene  OPI1  can improve the secretion capacity of full-length antibodies up to fourfold. Based on wild-type and ER-enlarged yeast strains, we conducted a screening of a folding factor overexpression library to identify proteins and their expression levels that enhance the secretion of antibodies. Out of six genes tested, addition of the peptidyl-prolyl isomerase  CPR5  provided the most beneficial effect on specific product yield while  PDI1 ,  ERO1 ,  KAR2 ,  LHS1  and  SIL1  had a mild or even negative effect to antibody secretion efficiency. Combining genes for ER enhancement did not induce any significant additional effect compared to addition of just one element. By combining the Δ opi1  strain, with the enlarged ER, with  CPR5  overexpression, we were able to boost the specific antibody product yield by a factor of 10 relative to the non-engineered strain.    Conclusions  Engineering protein folding in vivo is a major task for biopharmaceuticals production in yeast and needs to be optimized at several levels. By rational strain design and high-throughput screening applications we were able to increase the specific secreted antibody yields of  S. cerevisiae  up to 10-fold, providing a promising strain for further process optimization and platform development for antibody production.    Electronic supplementary material  The online version of this article (doi:10.1186/s12934-016-0488-5) contains supplementary material, which is available to authorized users.

Enhancing antibody folding and secretion by tailoring the Saccharomyces cerevisiae endoplasmic reticulum