Evidence map›Paper›PMID 29942079›Full record

ArticleNature chemical biology2018

Metabolic engineering of a carbapenem antibiotic synthesis pathway in Escherichia coli.

Helena Shomar, Sophie Gontier, Niels J F van den Broek, Héctor Tejeda Mora, Marek J Noga, Peter-Leon Hagedoorn, Gregory Bokinsky

Abstract read
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In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Molecules (Basel, Switzerland) · 2022
    Article
  6. Synthetic Biology Tools for Engineering Microbial Cells to Fight Superbugs.Frontiers in bioengineering and biotechnology · 2022
    Review
  7. Review
  8. Article
  9. 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

7 authors at 2 institutions in 2 countries.

Helena ShomarDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
Sophie GontierCentre for Research and Interdisciplinarity (CRI), Paris Descartes University, Paris, France.
Niels J F van den BroekDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
Héctor Tejeda MoraDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
Marek J NogaDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands.
Peter-Leon HagedoornDepartment of Biotechnology, Delft University of Technology, Delft, the Netherlands.
Gregory BokinskyDepartment of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, the Netherlands. G.E.Bokinsky@tudelft.nl.
Delft University of Technology · NLCenter for Research and Interdisciplinarity · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Carbapenems, a family of β-lactam antibiotics, are among the most powerful bactericidal compounds in clinical use. However, as rational engineering of native carbapenem-producing microbes is not currently possible, the present carbapenem supply relies upon total chemical synthesis of artificial carbapenem derivatives. To enable access to the full diversity of natural carbapenems, we have engineered production of a simple carbapenem antibiotic within Escherichia coli. By increasing concentrations of precursor metabolites and identifying a reducing cofactor of a bottleneck enzyme, we improved productivity by 60-fold over the minimal pathway and surpassed reported titers obtained from carbapenem-producing Streptomyces species. We stabilized E. coli metabolism against antibacterial effects of the carbapenem product by artificially inhibiting membrane synthesis, which further increased antibiotic productivity. As all known naturally occurring carbapenems are derived from a common intermediate, our engineered strain provides a platform for biosynthesis of tailored carbapenem derivatives in a genetically tractable and fast-growing species.

Indexed as

Metabolic EngineeringCarbapenemsEscherichia coliCarbapenems

Identifiers

PMID29942079
OpenAlexW2808779217

What OpenQuestion holds

Textmetadata
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.