Evidence map›Paper›PMID 31896772›Full record

ArticleNature communications2020

Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion.

Jahir M Gutierrez, Amir Feizi, Shangzhong Li, Thomas B Kallehauge, Hooman Hefzi, Lise M Grav, Daniel Ley, Deniz Baycin Hizal, Michael J Betenbaugh, Bjorn Voldborg and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
6.8field-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

64 citing papers in PubMed, 134 citations in OpenAlex.

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  17. The Power of Yeast.Yeast (Chichester, England) · 2025
    Review
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  20. Review

4 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

15 authors at 4 institutions in 3 countries.

Jahir M GutierrezDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Amir FeiziDepartment of Biology and Biological Engineering, Kemivägen 10, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden.
Shangzhong LiDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Thomas B KallehaugeNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Hooman HefziDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Lise M GravNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Daniel LeyNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Deniz Baycin HizalPharmaceutical R&D Department, Turgut Illaclari A.S, Istanbul, Turkey.
Michael J BetenbaughDepartment of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218-2686, USA.
Bjorn VoldborgNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Helene Faustrup KildegaardNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.
Gyun Min LeeNovo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Kongens Lyngby, Denmark.ORCID http://orcid.org/0000-0002-9876-7378
Bernhard O PalssonDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0003-2357-6785
Jens NielsenDepartment of Biology and Biological Engineering, Kemivägen 10, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-9955-6003
Nathan E LewisDepartment of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA. nlewisres@ucsd.edu.ORCID http://orcid.org/0000-0001-7700-3654
Novo Nordisk Foundation · DKFoundation Center · USChalmers University of Technology · SEJohns Hopkins University · US

Funding

Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3M
NIGMS NIH HHS R35 GM119850
6 · The paper itself

Abstract

In mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster ovary cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology.

Indexed as

GenomeAnimalsBone Morphogenetic Protein 2CHO CellsComputer SimulationCricetulusGene Knockdown TechniquesHumansMammalsMiceProteinsRecombinant ProteinsReproducibility of ResultsSecretory PathwayBone Morphogenetic Protein 2ProteinsRecombinant Proteins

Identifiers

PMID31896772
PMCPMC6940358
OpenAlexW2997477803

What OpenQuestion holds

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LicenceCC BY
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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.