Evidence map›Paper›PMID 39576948›Full record

ArticleBiochemistry2024

New Insights into the Mechanism of Action of L-681,217, a Medicinally Promising Polyketide Inhibitor of Bacterial Protein Translation.

Alexander M Soohoo, Rolin A Aguilar, Heewon Cho, Thomas M Privalsky, Lin Liu, Khanh P Nguyen, Christopher T Walsh, Chaitan Khosla

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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.

Alexander M SoohooDepartment of Chemical Engineering, Stanford University, Stanford, California 94305, United States.
Rolin A AguilarSarafan ChEM-H, Stanford University, Stanford, California 94305, United States.
Heewon ChoDepartment of Chemistry, Stanford University, Stanford, California 94305, United States.
Thomas M PrivalskyDepartment of Chemistry, Stanford University, Stanford, California 94305, United States.
Lin LiuDepartment of Chemistry, Stanford University, Stanford, California 94305, United States.
Khanh P NguyenDepartment of Chemistry, Stanford University, Stanford, California 94305, United States.
Christopher T WalshSarafan ChEM-H, Stanford University, Stanford, California 94305, United States.ORCID 0000-0002-0355-1938
Chaitan KhoslaDepartment of Chemical Engineering, Stanford University, Stanford, California 94305, United States.ORCID 0000-0001-6529-495X

Funding

Mechanisms and Evolution of Assembly-Line Polyketide SynthasesR35GM141799 · NIGMS · STANFORD UNIVERSITY · PI CHAITAN KHOSLA · 2021 to 2026
$2.5M
500 MHz NMR Spectrometer System with High Sensitivity Cryoprobe and Automated Sample Changer for Biochemical ResearchS10OD028697 · OD · STANFORD UNIVERSITY · PI BURNS, NOAH ZACHARY · 2020 to 2020
$709k
NIGMS NIH HHS R35 GM141799NIH HHS S10 OD028697
6 · The paper itself

Abstract

An attractive strategy for combating antibacterial resistance involves the development of new antibiotics whose mechanisms differ from those of existing ones in the clinic. Elfamycin antibiotics, whose prototypes include kirromycin and aurodox, are illustrative examples based on their ability to target EF-Tu, an essential component for protein translation in bacteria. Our efforts to revisit this antibiotic class were enabled by two developments. First, we produced L-681,217, an understudied member of this polyketide family harboring a terminal carboxylic acid in place of a hydroxypyridone ring, and synthesized a biotinylated derivative with comparable activity to the natural product. Second, we established a sensitive cell-free protein synthesis (CFPS) assay in which superfolder green fluorescent protein (sfGFP) production was inhibited by L-681,217. Biotinyl-L-681,217 was used to drain the CFPS system of endogenous EF-Tu, allowing replenishment with orthologs to interrogate pathogen selectivity and propensity toward resistance. Comparative

Indexed as

Anti-Bacterial AgentsPolyketidesProtein BiosynthesisBacterial ProteinsEscherichia coliProtein Synthesis InhibitorsAnti-Bacterial AgentsBacterial ProteinsPolyketidesProtein Synthesis Inhibitors

Identifiers

PMID39576948
PMCPMC11871046

What OpenQuestion holds

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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.