Following nature's roadmap: folding factors from plasma cells led to improvements in antibody secretion in S. cerevisiae

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Following nature's roadmap : folding factors from plasma cells led to improvements in antibody secretion in S. cerevisiae. / Koskela, Essi V.; de Ruijter, Jorg C.; Frey, Alexander D.

In: BIOTECHNOLOGY JOURNAL, Vol. 12, No. 8, 1600631, 01.08.2017.

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@article{5acf6a1e68fe44a588e8d32e7e72d9bd,
title = "Following nature's roadmap: folding factors from plasma cells led to improvements in antibody secretion in S. cerevisiae",
abstract = "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.",
keywords = "Antibodies, Protein folding, Synthetic biology, Yeast",
author = "Koskela, {Essi V.} and {de Ruijter}, {Jorg C.} and Frey, {Alexander D.}",
year = "2017",
month = "8",
day = "1",
doi = "10.1002/biot.201600631",
language = "English",
volume = "12",
journal = "BIOTECHNOLOGY JOURNAL",
issn = "1860-6768",
number = "8",

}

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TY - JOUR

T1 - Following nature's roadmap

T2 - folding factors from plasma cells led to improvements in antibody secretion in S. cerevisiae

AU - Koskela, Essi V.

AU - de Ruijter, Jorg C.

AU - Frey, Alexander D.

PY - 2017/8/1

Y1 - 2017/8/1

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://www.scopus.com/inward/record.url?scp=85019898032&partnerID=8YFLogxK

U2 - 10.1002/biot.201600631

DO - 10.1002/biot.201600631

M3 - Article

VL - 12

JO - BIOTECHNOLOGY JOURNAL

JF - BIOTECHNOLOGY JOURNAL

SN - 1860-6768

IS - 8

M1 - 1600631

ER -

ID: 15227152