Evidence map›Paper›PMID 38981108›Full record

ArticleJournal of the American Chemical Society2024

Cryptic Cerulenin Rearrangement in Ketosynthase Covalent Inhibition.

Ziran Jiang, Jeffrey A Chen, Osama G Mohamed, Jennifer Huynh, Aochiu Chen, Ashootosh Tripathi, James J La Clair, Michael D Burkart

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Ziran JiangDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
Jeffrey A ChenDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
Osama G MohamedNatural product Discovery Core - Life Sciences Institute, University of Michigan, Mary Sue Coleman Hall, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109, United States.ORCID 0000-0003-3216-6948
Jennifer HuynhDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
Aochiu ChenDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.ORCID 0000-0002-9143-7392
Ashootosh TripathiNatural product Discovery Core - Life Sciences Institute, University of Michigan, Mary Sue Coleman Hall, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109, United States.ORCID 0000-0003-2297-8088
James J La ClairDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
Michael D BurkartDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.ORCID 0000-0002-4472-2254

Funding

Protein-Protein Interactions in Natural Product BiosynthesisR01GM095970 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BURKART, MICHAEL D. · 2012 to 2025
$5.9M
NIGMS NIH HHS R01 GM095970
6 · The paper itself

Abstract

The antibiotic cerulenin is a fungal natural product identified as a covalent inhibitor of ketosynthases within fatty acid and polyketide biosynthesis. Due to its selective and potent inhibitory activity, cerulenin has found significant utility in multidisciplinary biochemical, biomedical, and clinical studies. Although its covalent inhibition profile has been confirmed, cerulenin's mechanism has not been fully determined at a molecular level, frustrating the drug development of related analogues. Herein, we describe the use of stable isotopic tracking with NMR and MS methods to unravel the covalent mechanism of cerulenin against type II fatty acid ketosynthases. We detail the discovery of a unique C2-C3 retro-aldol bond cleavage and a structural rearrangement upon covalent inhibition of cerulenin at the active cysteine residue in

Indexed as

CeruleninAnti-Bacterial AgentsEnzyme InhibitorsEscherichia coliFatty Acid Synthase, Type IIModels, MolecularMolecular StructureAnti-Bacterial AgentsCeruleninEnzyme InhibitorsFatty Acid Synthase, Type II

Identifiers

PMID38981108
PMCPMC12327055

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Registered trials

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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.