Evidence map›Paper›PMID 36351243›Full record

ArticleJournal of the American Chemical Society2022

Enzymatic Pyridine Aromatization during Thiopeptide Biosynthesis.

Andrew J Rice, Jarrett M Pelton, Nicholas J Kramer, Daniel S Catlin, Satish K Nair, Taras V Pogorelov, Douglas A Mitchell, Albert A Bowers

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Modular Synthesis of Pyritide-Inspired Macrocycles Featuring Bipyridine Motifs.Angewandte Chemie (International ed. in English) · 2025
    Article
  3. Peptidic Tryptophan Halogenation by a Promiscuous Flavin-Dependent Enzyme.Angewandte Chemie (International ed. in English) · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Review
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 2 institutions in 1 country.

Andrew J RiceDepartment of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.ORCID 0000-0001-8794-3826
Jarrett M PeltonDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0002-5483-9915
Nicholas J KramerDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Chapel Hill, North Carolina 27599, United States.
Daniel S CatlinDepartment of Biochemistry, Center for Biophysics and Quantitative Biology, University of Illinois, Urbana, Illinois 61801, United States.
Satish K NairCarl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 West Gregory Drive, Urbana, Illinois 61801, United States.ORCID 0000-0003-1790-1334
Taras V PogorelovDepartment of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.ORCID 0000-0001-5851-7721
Douglas A MitchellDepartment of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.ORCID 0000-0002-9564-0953
Albert A BowersDivision of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Chapel Hill, North Carolina 27599, United States.ORCID 0000-0001-8214-7484
University of Illinois Urbana-Champaign · USUniversity of North Carolina at Chapel Hill · US

Funding

Training Program at the Chemistry Biology InterfaceT32GM136629 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Paul Hergenrother · 2020 to 2026
$4.5M
Enzyme Chemistry and Biological Function of RiPP-like Modifications.R01GM097142 · NIGMS · VANDERBILT UNIVERSITY · PI MITCHELL, DOUGLAS ALAN · 2012 to 2024
$4.1M
MIRA Equipment SupplementR35GM125005 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Albert A Bowers · 2017 to 2026
$3.9M
Structural Biological Studies of Thipeptide Biosynthesis and EngineeringR01GM131347 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI NAIR, SATISH K · 2019 to 2022
$1.2M
NIGMS NIH HHS R01 GM097142NIGMS NIH HHS R01 GM131347NIGMS NIH HHS R35 GM125005NIGMS NIH HHS T32 GM136629
6 · The paper itself

Abstract

Thiazole-containing pyritides (thiopeptides) are ribosomally synthesized and post-translationally modified peptides (RiPPs) that have attracted interest owing to their potent biological activities and structural complexity. The class-defining feature of a thiopeptide is a six-membered, nitrogenous heterocycle formed by an enzymatic [4 + 2]-cycloaddition. In rare cases, piperidine or dehydropiperidine (DHP) is present; however, the aromatized pyridine is considerably more common. Despite significant effort, the mechanism by which the central pyridine is formed remains poorly understood. Building on our recent observation of the Bycroft-Gowland intermediate (i.e., the direct product of the [4 + 2]-cycloaddition), we interrogated thiopeptide pyridine synthases using a combination of targeted mutagenesis, kinetic assays, substrate analogs, enzyme-substrate cross-linking, and chemical rescue experiments. Collectively, our data delineate roles for several conserved residues in thiopeptide pyridine synthases. A critical tyrosine facilitates the final aromatization step of pyridine formation. This work provides a foundation for further exploration of the [4 + 2]-cycloaddition reaction and future customization of pyridine-containing macrocyclic peptides.

Indexed as

PeptidesThiazolesCycloaddition ReactionPyridinesPeptidesPyridinesThiazoles

Identifiers

PMID36351243
PMCPMC9955758
OpenAlexW4308687250

What OpenQuestion holds

Textmetadata
LicenceTDM
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.