Evidence map›Paper›PMID 40504771›Full record

ArticlePLoS biology2025

Genome mining based on transcriptional regulatory networks uncovers a novel locus involved in desferrioxamine biosynthesis.

Hannah E Augustijn, Zachary L Reitz, Le Zhang, Jeanine A Boot, Somayah S Elsayed, Gregory L Challis, Marnix H Medema, Gilles P van Wezel

Abstract read
In one paragraph

Article in PLoS biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Hannah E AugustijnBioinformatics Group, Wageningen University, Wageningen, The Netherlands.
Zachary L ReitzBioinformatics Group, Wageningen University, Wageningen, The Netherlands.
Le ZhangInstitute of Biology, Leiden University, Leiden, The Netherlands.
Jeanine A BootBioinformatics Group, Wageningen University, Wageningen, The Netherlands.
Somayah S ElsayedInstitute of Biology, Leiden University, Leiden, The Netherlands.
Gregory L ChallisDepartment of Chemistry, University of Warwick, Coventry, United Kingdom.
Marnix H MedemaBioinformatics Group, Wageningen University, Wageningen, The Netherlands.
Gilles P van WezelInstitute of Biology, Leiden University, Leiden, The Netherlands.ORCID 0000-0003-0341-1561

Funding

European Union ERC AdvancedEuropean Union ERC Starting
6 · The paper itself

Abstract

Bacteria produce a plethora of natural products that are in clinical, agricultural and biotechnological use. Genome mining has uncovered millions of biosynthetic gene clusters (BGCs) that encode their biosynthesis, the vast majority of them lacking a clear product or function. Thus, a major challenge is to predict the bioactivities of the molecules these BGCs specify, and how to elicit their expression. Here, we present an innovative strategy whereby we harness the power of regulatory networks combined with global gene expression patterns to predict BGC functions. Bioinformatic analysis of all genes predicted to be controlled by the iron master regulator DmdR1 combined with co-expression data, led to identification of the novel operon desJGH that plays a key role in the biosynthesis of the iron overload drug desferrioxamine (DFO) B in Streptomyces coelicolor. Deletion of either desG or desH strongly reduces the biosynthesis of DFO B, while that of DFO E is enhanced. DesJGH most likely act by changing the balance between the DFO precursors. Our work shows the power of harnessing regulation-based genome mining to functionally prioritize BGCs, accelerating the discovery of novel bioactive molecules.

Indexed as

DeferoxamineGene Regulatory NetworksGenome, BacterialStreptomyces coelicolorBacterial ProteinsComputational BiologyData MiningGene Expression Regulation, BacterialIronMultigene FamilyOperonBacterial ProteinsDeferoxamineIron

Identifiers

PMID40504771
PMCPMC12161575

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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.