ArticleEukaryotic cell2012
The Aspergillus fumigatus protein GliK protects against oxidative stress and is essential for gliotoxin biosynthesis.
Article in Eukaryotic cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Gliotoxin Production and Self-Defense in Filamentous Fungi.Annual review of microbiology · 2025Review
- Progress in Gliotoxin Research.Molecules (Basel, Switzerland) · 2025Review
- A Review of Novel Antioxidant Ergothioneine: Biosynthesis Pathways, Production, Function and Food Applications.Foods (Basel, Switzerland) · 2025Review
- Biosynthesis of ergothioneine: current state, achievements, and perspectives.Applied microbiology and biotechnology · 2025Review
- Genome mining and biosynthetic pathways of marine-derived fungal bioactive natural products.Frontiers in microbiology · 2024Review
- Antifungal properties of cathelicidin LL-37: current knowledge and future research directions.World journal of microbiology & biotechnology · 2023Review
- Gliotoxin and related metabolites as zinc chelators: implications and exploitation to overcome antimicrobial resistance.Essays in biochemistry · 2023Article
- Methionine biosynthesis enzyme MoMet2 is required for rice blast fungus pathogenicity by promoting virulence gene expression via reducing 5mC modification.PLoS genetics · 2023Article
- Histone 2-Hydroxyisobutyryltransferase Encoded byToxins · 2022Article
- Epipolythiodioxopiperazine-Based Natural Products: Building Blocks, Biosynthesis and Biological Activities.Chembiochem : a European journal of chemical biology · 2022Review
- Stress Responses Elicited by Glucose Withdrawal inJournal of fungi (Basel, Switzerland) · 2022Article
- A SingleInternational journal of molecular sciences · 2022Article
- Ergothioneine, Ovothiol A, and Selenoneine-Histidine-Derived, Biologically Significant, Trace Global Alkaloids.Molecules (Basel, Switzerland) · 2022Review
- Exposure to theMicrobiology (Reading, England) · 2022Article
- The Toxic Mechanism of Gliotoxins and Biosynthetic Strategies for Toxicity Prevention.International journal of molecular sciences · 2021Review
- The Peroxiredoxin Asp f3 Acts as Redox Sensor inGenes · 2021Article
- Article
- The biology of ergothioneine, an antioxidant nutraceutical.Nutrition research reviews · 2020Review
- The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence.PLoS pathogens · 2020Article
- Article
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8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of a number of genes in the gliotoxin biosynthetic cluster (gli) in Aspergillus fumigatus remains unknown. Here, we demonstrate that gliK deletion from two strains of A. fumigatus completely abolished gliotoxin biosynthesis. Furthermore, exogenous H(2)O(2) (1 mM), but not gliotoxin, significantly induced A. fumigatus gliK expression (P = 0.0101). While both mutants exhibited significant sensitivity to both exogenous gliotoxin (P < 0.001) and H(2)O(2) (P < 0.01), unexpectedly, exogenous gliotoxin relieved H(2)O(2)-induced growth inhibition in a dose-dependent manner (0 to 10 μg/ml). Gliotoxin-containing organic extracts derived from A. fumigatus ATCC 26933 significantly inhibited (P < 0.05) the growth of the ΔgliK(26933) deletion mutant. The A. fumigatus ΔgliK(26933) mutant secreted metabolites, devoid of disulfide linkages or free thiols, that were detectable by reverse-phase high-performance liquid chromatography and liquid chromatography-mass spectrometry with m/z 394 to 396. These metabolites (m/z 394 to 396) were present at significantly higher levels in the culture supernatants of the A. fumigatus ΔgliK(26933) mutant than in those of the wild type (P = 0.0024 [fold difference, 24] and P = 0.0003 [fold difference, 9.6], respectively) and were absent from A. fumigatus ΔgliG. Significantly elevated levels of ergothioneine were present in aqueous mycelial extracts of the A. fumigatus ΔgliK(26933) mutant compared to the wild type (P < 0.001). Determination of the gliotoxin uptake rate revealed a significant difference (P = 0.0045) between that of A. fumigatus ATCC 46645 (9.3 pg/mg mycelium/min) and the ΔgliK(46645) mutant (31.4 pg/mg mycelium/min), strongly suggesting that gliK absence and the presence of elevated ergothioneine levels impede exogenously added gliotoxin efflux. Our results confirm a role for gliK in gliotoxin biosynthesis and reveal new insights into gliotoxin functionality in A. fumigatus.
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