Evidence map›Paper›PMID 29309054›Full record

ArticleNature chemical biology2018

Mechanism of intersubunit ketosynthase-dehydratase interaction in polyketide synthases.

Matthew Jenner, Simone Kosol, Daniel Griffiths, Panward Prasongpholchai, Lucio Manzi, Andrew S Barrow, John E Moses, Neil J Oldham, Józef R Lewandowski, Gregory L Challis

Open access · greenAbstract read
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 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Total Synthesis ofJournal of the American Chemical Society · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Structure and Function of the α-Hydroxylation Bimodule of the Mupirocin Polyketide Synthase.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Docking domain-mediated subunit interactions in natural product megasynth(et)ases.Journal of industrial microbiology & biotechnology · 2021
    Review
  16. Dipolar Order Parameters in Large Systems With Fast Spinning.Frontiers in molecular biosciences · 2021
    Article
  17. Synthetic biology enabling access to designer polyketides.Current opinion in chemical biology · 2020
    Review
  18. Review
  19. Article
  20. 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

10 authors at 2 institutions in 1 country.

Matthew JennerDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
Simone KosolDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UK.ORCID 0000-0001-7913-4818
Daniel GriffithsDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
Panward PrasongpholchaiDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
Lucio ManziSchool of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK.
Andrew S BarrowSchool of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK.
John E MosesSchool of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK.
Neil J OldhamSchool of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK.
Józef R LewandowskiDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UK.ORCID 0000-0001-6525-7083
Gregory L ChallisDepartment of Chemistry, University of Warwick, Coventry CV4 7AL, UK.ORCID 0000-0001-5976-3545
University of Warwick · GBUniversity of Nottingham · GB

Funding

Biotechnology and Biological Sciences Research Council BB/L021692/1Biotechnology and Biological Sciences Research Council BB/L022761/1Biotechnology and Biological Sciences Research Council BB/M017982/1European Research Council 639907
6 · The paper itself

Abstract

Modular polyketide synthases (PKSs) produce numerous structurally complex natural products that have diverse applications in medicine and agriculture. PKSs typically consist of several multienzyme subunits that utilize structurally defined docking domains (DDs) at their N and C termini to ensure correct assembly into functional multiprotein complexes. Here we report a fundamentally different mechanism for subunit assembly in trans-acyltransferase (trans-AT) modular PKSs at the junction between ketosynthase (KS) and dehydratase (DH) domains. This mechanism involves direct interaction of a largely unstructured docking domain (DD) at the C terminus of the KS with the surface of the downstream DH. Acyl transfer assays and mechanism-based crosslinking established that the DD is required for the KS to communicate with the acyl carrier protein appended to the DH. Two distinct regions for binding of the DD to the DH were identified using NMR spectroscopy, carbene footprinting, and mutagenesis, providing a foundation for future elucidation of the molecular basis for interaction specificity.

Indexed as

Protein BindingAcyl Carrier ProteinAcyltransferasesBacteriaCross-Linking ReagentsHydro-LyasesLyasesMagnetic Resonance SpectroscopyMarkov ChainsMethaneMutagenesisPhylogenyPolyketide SynthasesProtein DomainsProtein Structure, SecondaryAcyl Carrier ProteinAcyltransferasescarbeneCross-Linking ReagentsHydro-LyasesLyasesMethanePolyketide Synthases

Identifiers

PMID29309054
PMCPMC5846730
OpenAlexW2772263299

What OpenQuestion holds

Textmetadata
LicenceTDM
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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.