TY - JOUR
T1 - Following nature's roadmap
T2 - folding factors from plasma cells led to improvements in antibody secretion in S. cerevisiae
AU - Koskela, EV
AU - de Ruijter, Jorg
AU - Frey, AD
PY - 2017/8
Y1 - 2017/8
N2 - Therapeutic protein production in yeast is a reality in industry with an untapped potential to expand to more complex proteins, such as full-length antibodies. Despite numerous engineering approaches, cellular limitations are preventing the use of Saccharomyces cerevisiae as the titers of recombinant antibodies are currently not competitive. Instead of a host specific approach, the possibility of adopting the features from native producers of antibodies, plasma cells, to improve antibody production in yeast. A subset of mammalian folding factors upregulated in plasma cells for expression in yeast and screened for beneficial effects on antibody secretion using a high-throughput ELISA platform was selected. Co-expression of the mammalian chaperone BiP, the co-chaperone GRP170, or the peptidyl-prolyl isomerase FKBP2, with the antibody improved specific product yields up to two-fold. By comparing strains expressing FKBP2 or the yeast PPIase Cpr5p, the authors demonstrate that speeding up peptidyl-prolyl isomerization by upregulation of catalyzing enzymes is a key factor to improve antibody titers in yeast. The findings show that following the route of plasma cells can improve product titers and contribute to developing an alternative yeast-based antibody factory.
AB - Therapeutic protein production in yeast is a reality in industry with an untapped potential to expand to more complex proteins, such as full-length antibodies. Despite numerous engineering approaches, cellular limitations are preventing the use of Saccharomyces cerevisiae as the titers of recombinant antibodies are currently not competitive. Instead of a host specific approach, the possibility of adopting the features from native producers of antibodies, plasma cells, to improve antibody production in yeast. A subset of mammalian folding factors upregulated in plasma cells for expression in yeast and screened for beneficial effects on antibody secretion using a high-throughput ELISA platform was selected. Co-expression of the mammalian chaperone BiP, the co-chaperone GRP170, or the peptidyl-prolyl isomerase FKBP2, with the antibody improved specific product yields up to two-fold. By comparing strains expressing FKBP2 or the yeast PPIase Cpr5p, the authors demonstrate that speeding up peptidyl-prolyl isomerization by upregulation of catalyzing enzymes is a key factor to improve antibody titers in yeast. The findings show that following the route of plasma cells can improve product titers and contribute to developing an alternative yeast-based antibody factory.
KW - Antibodies
KW - Protein folding
KW - Synthetic biology
KW - Yeast
UR - http://europepmc.org/abstract/med/28429845
UR - http://www.scopus.com/inward/record.url?scp=85019898032&partnerID=8YFLogxK
U2 - 10.1002/biot.201600631
DO - 10.1002/biot.201600631
M3 - Article
C2 - 28429845
SN - 1860-6768
VL - 12
JO - Biotechnology Journal
JF - Biotechnology Journal
IS - 8
M1 - 1600631
ER -