Evidence map›Paper›PMID 24853352›Full record

ArticleMetabolic engineering2014

Model based engineering of Pichia pastoris central metabolism enhances recombinant protein production.

Justyna Nocon, Matthias G Steiger, Martin Pfeffer, Seung Bum Sohn, Tae Yong Kim, Michael Maurer, Hannes Rußmayer, Stefan Pflügl, Magnus Ask, Christina Haberhauer-Troyer and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Metabolic engineering, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

67 citing papers in PubMed, 139 citations in OpenAlex.

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  19. Current advances ofFrontiers in microbiology · 2022
    Review
  20. Microorganisms · 2021
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7 more citing papers are in PubMed but not listed here.

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

16 authors at 4 institutions in 2 countries.

Justyna NoconDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria.
Matthias G SteigerDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Martin PfefferDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria.
Seung Bum SohnBioinformatics Research Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Tae Yong KimBioinformatics Research Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Michael MaurerSchool of Bioengineering, University of Applied Sciences FH Campus Wien, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Hannes RußmayerDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Stefan PflüglDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Magnus AskDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Christina Haberhauer-TroyerAustrian Centre of Industrial Biotechnology, Vienna, Austria; Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.
Karin OrtmayrDepartment of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.
Stephan HannAustrian Centre of Industrial Biotechnology, Vienna, Austria; Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.
Gunda KoellenspergerAustrian Centre of Industrial Biotechnology, Vienna, Austria; Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria.
Brigitte GasserDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Vienna, Austria.
Sang Yup LeeBioinformatics Research Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; Metabolic Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 plus program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Diethard MattanovichDepartment of Biotechnology, University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Vienna, Austria. Electronic address: diethard.mattanovich@boku.ac.at.
BOKU University · ATAustrian Centre of Industrial Biotechnology (Austria) · ATKorea Advanced Institute of Science and Technology · KRFH Campus Wien · AT

Funding

Austrian Science Fund FWF W 1224
6 · The paper itself

Abstract

The production of recombinant proteins is frequently enhanced at the levels of transcription, codon usage, protein folding and secretion. Overproduction of heterologous proteins, however, also directly affects the primary metabolism of the producing cells. By incorporation of the production of a heterologous protein into a genome scale metabolic model of the yeast Pichia pastoris, the effects of overproduction were simulated and gene targets for deletion or overexpression for enhanced productivity were predicted. Overexpression targets were localized in the pentose phosphate pathway and the TCA cycle, while knockout targets were found in several branch points of glycolysis. Five out of 9 tested targets led to an enhanced production of cytosolic human superoxide dismutase (hSOD). Expression of bacterial β-glucuronidase could be enhanced as well by most of the same genetic modifications. Beneficial mutations were mainly related to reduction of the NADP/H pool and the deletion of fermentative pathways. Overexpression of the hSOD gene itself had a strong impact on intracellular fluxes, most of which changed in the same direction as predicted by the model. In vivo fluxes changed in the same direction as predicted to improve hSOD production. Genome scale metabolic modeling is shown to predict overexpression and deletion mutants which enhance recombinant protein production with high accuracy.

Indexed as

Metabolic EngineeringModels, BiologicalPichiaCitric Acid CycleGene ExpressionGlycolysisHumansMetabolomeNADRecombinant ProteinsSuperoxide DismutaseSuperoxide Dismutase-1NADRecombinant ProteinsSOD1 protein, humanSuperoxide DismutaseSuperoxide Dismutase-1Flux analysisGEMMetabolic modelingNADPHRecombinant proteinYeast

Identifiers

PMID24853352
PMCPMC4094982
OpenAlexW2016229032

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.