Evidence map›Paper›PMID 40474245›Full record

ArticleMicrobial cell factories2025

Eliminating viscosity challenges in continuous cultivation of yeast producing a GLP-1 like peptide.

Ioannis Voulgaris, Anders Nygaard Nielsen, Tine Petersen, Sanne Jensen

Abstract read
In one paragraph

Article in Microbial cell factories, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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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

1 citing paper in PubMed.

  1. Article
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

4 authors.

Ioannis VoulgarisRecombinant Drug Research, Novo Nordisk A/S, Novo Park Alle, Novo Nordisk Park 1, 2760, Måløv, Denmark. ivo@novonordisk.com.ORCID http://orcid.org/0000-0001-8367-3224
Anders Nygaard NielsenRecombinant Drug Research, Novo Nordisk A/S, Novo Park Alle, Novo Nordisk Park 1, 2760, Måløv, Denmark.
Tine PetersenRecombinant Drug Research, Novo Nordisk A/S, Novo Park Alle, Novo Nordisk Park 1, 2760, Måløv, Denmark.
Sanne JensenRecombinant Drug Research, Novo Nordisk A/S, Novo Park Alle, Novo Nordisk Park 1, 2760, Måløv, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe emergence of GLP-1s for the treatment of diabetes, obesity and other diseases has led to increased focus on finding efficient ways to produce the peptides in sufficient amounts to satisfy the ever-increasing demand. Although the use of microbial hosts constitutes the cheapest, easiest and safest way to produce these peptides in high volumes, process challenges still exist that reduce the production capacity. One of the main production challenges is the high viscosity of cultivation broths, which reduces the mass and oxygen transfer, thereby creating substrate and oxygen gradients that potentially lead to unwanted secondary metabolism and eventually compromises capacity.

resultsThe methodology used to identify the underlying factors of highly viscous broths during the recombinant production of GLP-1 precursors in S. cerevisiae in continuous cultivation is presented. Two root causes leading to highly viscous broths were uncovered and solutions identified. The first one is found in the soluble fraction of the broth and relates to the aggregation of GLP-1 precursor molecules that leads to highly viscous, shear thinning cultivation broths. The cultivation conditions under which the aggregation occurs and the consequences for both cultivation and product recovery are discussed. The second source of viscosity is found in the insoluble fraction of the cultivation broth and relates to cell aggregation due to Amn1p dependent incomplete separation of mother and daughter cells. This type of cell aggregation causes formation of cell clumps and leads to high viscosity cultivation broths with mild shear thickening properties.

conclusionsTo eliminate the GLP-1 peptide related viscosity, a new generation of yeast host strains that tolerates cultivation at increased pH values, above those that cause GLP-1 precursor aggregation, were utilized. In the case of the cell derived viscosity, yeast strains carrying either a deletion of the AMN1 gene or integration of the non-clumping AMN1

Indexed as

Glucagon-Like Peptide 1Saccharomyces cerevisiaeCulture MediaRecombinant ProteinsViscosityCulture MediaGlucagon-Like Peptide 1Recombinant ProteinsAggregationAMN1FermentationFlocculationGLP-1S. cerevisiaeViscosity

Identifiers

PMID40474245
PMCPMC12142998

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.