Evidence map›Paper›PMID 28100236›Full record

ArticleMicrobial cell factories2017

Human β-defensin-2 production from S. cerevisiae using the repressible MET17 promoter.

Thea S B Møller, Joanna Hay, Malcolm J Saxton, Karen Bunting, Evamaria I Petersen, Søren Kjærulff, Christopher J A Finnis

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

7 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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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

7 authors at 2 institutions in 2 countries.

Thea S B MøllerNovozymes Biopharma UK Limited, Castle Court, 59 Castle Boulevard, Nottingham, NG7 1FD, UK.
Joanna HayNovozymes Biopharma UK Limited, Castle Court, 59 Castle Boulevard, Nottingham, NG7 1FD, UK.
Malcolm J SaxtonNovozymes Biopharma UK Limited, Castle Court, 59 Castle Boulevard, Nottingham, NG7 1FD, UK.
Karen BuntingNovozymes Biopharma UK Limited, Castle Court, 59 Castle Boulevard, Nottingham, NG7 1FD, UK.
Evamaria I PetersenDepartment of Physics and Nanotechnology, Aalborg University, Skjernvej 4A, Aalborg East, 9220, Aalborg, Denmark.
Søren KjærulffNovozymes Biopharma UK Limited, Castle Court, 59 Castle Boulevard, Nottingham, NG7 1FD, UK.
Christopher J A FinnisNovozymes Biopharma UK Limited, Castle Court, 59 Castle Boulevard, Nottingham, NG7 1FD, UK. chrisfinnis@hotmail.com.
Novozymes (United Kingdom) · GBAalborg University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBaker's yeast Saccharomyces cerevisiae is a proven host for the commercial production of recombinant biopharmaceutical proteins. For the manufacture of heterologous proteins with activities deleterious to the host it can be desirable to minimise production during the growth phase and induce production late in the exponential phase. Protein expression by regulated promoter systems offers the possibility of improving productivity in this way by separating the recombinant protein production phase from the yeast growth phase. Commonly used inducible promoters do not always offer convenient solutions for industrial scale biopharmaceutical production with engineered yeast systems.

resultsHere we show improved secretion of the antimicrobial protein, human β-defensin-2, (hBD2), using the S. cerevisiae MET17 promoter by repressing expression during the growth phase. In shake flask culture, a higher final concentration of human β-defensin-2 was obtained using the repressible MET17 promoter system than when using the strong constitutive promoter from proteinase B (PRB1) in a yeast strain developed for high-level commercial production of recombinant proteins. Furthermore, this was achieved in under half the time using the MET17 promoter compared to the PRB1 promoter. Cell density, plasmid copy-number, transcript level and protein concentration in the culture supernatant were used to study the effects of different initial methionine concentrations in the culture media for the production of human β-defensin-2 secreted from S. cerevisiae.

conclusionsThe repressible S. cerevisiae MET17 promoter was more efficient than a strong constitutive promoter for the production of human β-defensin-2 from S. cerevisiae in small-scale culture and offers advantages for the commercial production of this and other heterologous proteins which are deleterious to the host organism. Furthermore, the MET17 promoter activity can be modulated by methionine alone, which has a safety profile applicable to biopharmaceutical manufacturing.

Indexed as

Gene Expression Regulation, FungalPromoter Regions, Geneticbeta-DefensinsCulture MediaCysteine SynthaseHumansMethioninePlasmidsRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSerine Endopeptidasesbeta-DefensinsCulture MediaCysteine SynthaseDEFB4A protein, humanMET17 protein, S cerevisiaeMethionineRecombinant ProteinsSaccharomyces cerevisiae ProteinsSerine Endopeptidasesyeast proteinase BHuman β-defensin-2MET17 promoterSaccharomyces cerevisiaeYeast

Identifiers

PMID28100236
PMCPMC5241953
OpenAlexW2571684253

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.