Evidence map›Paper›PMID 27216259›Full record

ArticleMicrobial cell factories2016

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

Jorg C de Ruijter, Essi V Koskela, Alexander D Frey

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
5.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 103 citations in OpenAlex.

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  12. Tailored UPRE2 variants for dynamic gene regulation in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  16. Expression ofEPJ web of conferences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Jorg C de RuijterDepartment of Biotechnology and Chemical Technology, Aalto University, Kemistintie 1, 02150, Espoo, Finland.
Essi V KoskelaDepartment of Biotechnology and Chemical Technology, Aalto University, Kemistintie 1, 02150, Espoo, Finland.
Alexander D FreyDepartment of Biotechnology and Chemical Technology, Aalto University, Kemistintie 1, 02150, Espoo, Finland. alexander.frey@aalto.fi.
Aalto University · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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.

resultsFollowing 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 Δopi1 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.

conclusionsEngineering 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.

Indexed as

AntibodiesEndoplasmic ReticulumPeptidylprolyl IsomerasePlasmidsPromoter Regions, GeneticProtein FoldingSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTemperatureAntibodiesPeptidylprolyl IsomeraseSaccharomyces cerevisiae ProteinsAntibodyChaperonesEndoplasmic reticulumHeterologous protein productionProtein folding

Identifiers

PMID27216259
PMCPMC4878073
OpenAlexW2408236302

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.