ArticleChembiochem : a European journal of chemical biology2020
Reporter-Guided Transposon Mutant Selection for Activation of Silent Gene Clusters in Burkholderia thailandensis.
Article in Chembiochem : a European journal of chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Transposon mutagenesis in bacterial natural product discovery.Essays in biochemistry · 2026Review
- Regulatory and metabolic control of microbial biosynthetic gene clusters.Communications biology · 2026Review
- A genetically tractable branch of environmental Pedobacter from the phylum Bacteroidota represents a hotspot for natural product discovery.Scientific reports · 2025Article
- Microbial secondary metabolites: advancements to accelerate discovery towards application.Nature reviews. Microbiology · 2025Review
- Modern Trends in Natural Antibiotic Discovery.Life (Basel, Switzerland) · 2023Review
- Biotechnology approaches for natural product discovery, engineering, and production based on Burkholderia bacteria.Current opinion in biotechnology · 2022Review
- Guidelines for metabolomics-guided transposon mutagenesis for microbial natural product discovery.Methods in enzymology · 2022Article
- Piperacillin triggers virulence factor biosynthesis via the oxidative stress response inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters.Annual review of biochemistry · 2021Review
- Employing chemical synthesis to study the structure and function of colibactin, a "dark matter" metabolite.Natural product reports · 2020Review
- Unlocking Cryptic Metabolites with Mass Spectrometry-Guided Transposon Mutant Selection.ACS chemical biology · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Most natural product biosynthetic gene clusters that can be observed bioinformatically are silent. This insight has prompted the development of several methodologies for inducing their expression. One of the more recent methods, termed reporter-guided mutant selection (RGMS), entails creation of a library of mutants that is then screened for the desired phenotype via reporter gene expression. Herein, we apply a similar approach to Burkholderia thailandensis and, using transposon mutagenesis, mutagenize three strains, each carrying a fluorescent reporter in the malleilactone (mal), capistruin (cap), or an unidentified ribosomal peptide (tomm) gene cluster. We show that even a small library of <500 mutants can be used to induce expression of each cluster. We also explore the mechanism of activation and find that inhibition of pyrimidine biosynthesis is linked to the induction of the mal cluster. Both a transposon insertion into pyrF as well as small-molecule-mediated inhibition of PyrF trigger malleilactone biosynthesis. Our results pave the way toward the broad application of RGMS and related approaches to Burkholderia spp.
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