Evidence map›Paper›PMID 25058475›Full record

ArticlePloS one2014

Apicidin F: characterization and genetic manipulation of a new secondary metabolite gene cluster in the rice pathogen Fusarium fujikuroi.

Eva-Maria Niehaus, Slavica Janevska, Katharina W von Bargen, Christian M K Sieber, Henning Harrer, Hans-Ulrich Humpf, Bettina Tudzynski

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

34 citing papers in PubMed, 69 citations in OpenAlex.

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  15. Anaerobic gut fungi are an untapped reservoir of natural products.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  16. Review
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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

7 authors at 2 institutions in 1 country.

Eva-Maria NiehausWestfälische Wilhelms-Universität Münster, Institut für Biologie und Biotechnologie der Pflanzen, Münster, Germany.
Slavica JanevskaWestfälische Wilhelms-Universität Münster, Institut für Biologie und Biotechnologie der Pflanzen, Münster, Germany.
Katharina W von BargenWestfälische Wilhelms-Universität Münster, Institut für Lebensmittelchemie, Münster, Germany.
Christian M K SieberHelmholtz Zentrum München (GmbH), Institut für Bioinformatik und Systembiologie, Neuherberg, Germany.
Henning HarrerWestfälische Wilhelms-Universität Münster, Institut für Lebensmittelchemie, Münster, Germany.
Hans-Ulrich HumpfWestfälische Wilhelms-Universität Münster, Institut für Lebensmittelchemie, Münster, Germany.
Bettina TudzynskiWestfälische Wilhelms-Universität Münster, Institut für Biologie und Biotechnologie der Pflanzen, Münster, Germany.
University of Münster · DEInstitute of Bioinformatics and Systems Biology · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The fungus F. fujikuroi is well known for its production of gibberellins causing the 'bakanae' disease of rice. Besides these plant hormones, it is able to produce other secondary metabolites (SMs), such as pigments and mycotoxins. Genome sequencing revealed altogether 45 potential SM gene clusters, most of which are cryptic and silent. In this study we characterize a new non-ribosomal peptide synthetase (NRPS) gene cluster that is responsible for the production of the cyclic tetrapeptide apicidin F (APF). This new SM has structural similarities to the known histone deacetylase inhibitor apicidin. To gain insight into the biosynthetic pathway, most of the 11 cluster genes were deleted, and the mutants were analyzed by HPLC-DAD and HPLC-HRMS for their ability to produce APF or new derivatives. Structure elucidation was carried out be HPLC-HRMS and NMR analysis. We identified two new derivatives of APF named apicidin J and K. Furthermore, we studied the regulation of APF biosynthesis and showed that the cluster genes are expressed under conditions of high nitrogen and acidic pH in a manner dependent on the nitrogen regulator AreB, and the pH regulator PacC. In addition, over-expression of the atypical pathway-specific transcription factor (TF)-encoding gene APF2 led to elevated expression of the cluster genes under inducing and even repressing conditions and to significantly increased product yields. Bioinformatic analyses allowed the identification of a putative Apf2 DNA-binding ("Api-box") motif in the promoters of the APF genes. Point mutations in this sequence motif caused a drastic decrease of APF production indicating that this motif is essential for activating the cluster genes. Finally, we provide a model of the APF biosynthetic pathway based on chemical identification of derivatives in the cultures of deletion mutants.

Indexed as

Multigene FamilyCloning, MolecularFungal ProteinsFusariumGene DeletionGene Expression Regulation, FungalHydrogen-Ion ConcentrationNitrogenPeptides, CyclicPoint MutationSecondary Metabolismapicidin FFungal ProteinsNitrogenPeptides, Cyclic

Identifiers

PMID25058475
PMCPMC4109984
OpenAlexW1969703332

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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.