Evidence map›Paper›PMID 33826886›Full record

ArticleCell reports2021

Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications.

Amitesh Anand, Connor A Olson, Anand V Sastry, Arjun Patel, Richard Szubin, Laurence Yang, Adam M Feist, Bernhard O Palsson

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.5field-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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 2026
    Review
  3. C6‑HSL enhances BPA tolerance inCurrent research in microbial sciences · 2026
    Article
  4. Article
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  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Regulation of phosphate starvation-specific responses inMicrobiology (Reading, England) · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Antioxidant Mechanism ofFrontiers in microbiology · 2022
    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

8 authors at 3 institutions in 4 countries.

Amitesh AnandDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Connor A OlsonDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Anand V SastryDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Arjun PatelDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Richard SzubinDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Laurence YangDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemical Engineering, Queen's University, Kingston, ON, Canada.
Adam M FeistDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, Building 220, 2800 Kongens, Lyngby, Denmark.
Bernhard O PalssonDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, Building 220, 2800 Kongens, Lyngby, Denmark. Electronic address: palsson@ucsd.edu.
University of California San Diego · USNovo Nordisk Foundation · DKQueen's University · CA

Funding

Systems Biology Approach to Redefine Susceptibility Testing and Treatment of MDR Pathogens in the Context of Host ImmunityU01AI124316 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 2016 to 2020
$10.2M
GENOMICALLY BASED MODELS FOR ANTIBIOTIC DEVELOPMENTR01GM057089 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 1998 to 2021
$6.9M
NIAID NIH HHS U01 AI124316NIGMS NIH HHS R01 GM057089
6 · The paper itself

Abstract

Pyruvate dehydrogenase complex (PDC) functions as the main determinant of the respiro-fermentative balance because it converts pyruvate to acetyl-coenzyme A (CoA), which then enters the TCA (tricarboxylic acid cycle). PDC is repressed by the pyruvate dehydrogenase complex regulator (PdhR) in Escherichia coli. The deletion of the pdhR gene compromises fitness in aerobic environments. We evolve the E. coli pdhR deletion strain to examine its achievable growth rate and the underlying adaptive strategies. We find that (1) optimal proteome allocation to PDC is critical in achieving optimal growth rate; (2) expression of PDC in evolved strains is reduced through mutations in the Shine-Dalgarno sequence; (3) rewiring of the TCA flux and increased reactive oxygen species (ROS) defense occur in the evolved strains; and (4) the evolved strains adapt to an efficient biomass yield. Together, these results show how adaptation can find alternative regulatory mechanisms for a key cellular process if the primary regulatory mode fails.

Indexed as

Binding SitesCitric Acid CycleElectronsEscherichia coliEscherichia coli ProteinsGlycolysisHomeostasisOxidation-ReductionPyruvate Dehydrogenase ComplexPyruvic AcidRibosomesTranscription, GeneticEscherichia coli ProteinsPyruvate Dehydrogenase ComplexPyruvic Acidadaptive laboratory evolutionbioenergeticsproteome allocationsystem biologytranscriptional regulatory network

Identifiers

PMID33826886
PMCPMC8489512
OpenAlexW3147358936

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.