ArticlePloS one2014
A proteomic approach to investigating gene cluster expression and secondary metabolite functionality in Aspergillus fumigatus.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
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- 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
- Coccidioides Species: A Review of Basic Research: 2022.Journal of fungi (Basel, Switzerland) · 2022Review
- Biologia futura: combinatorial stress responses in fungi.Biologia futura · 2022Review
- Fungal secondary metabolites in food and pharmaceuticals in the era of multi-omics.Applied microbiology and biotechnology · 2022Review
- At the metal-metabolite interface inMicrobiology (Reading, England) · 2021Article
- Phytoplankton trigger the production of cryptic metabolites in the marine actinobacterium Salinispora tropica.Microbial biotechnology · 2021Article
- TheMolecular & cellular proteomics : MCP · 2020Article
- L-Amino Acid Oxidases From Mushrooms Show Antibacterial Activity Against the PhytopathogenFrontiers in microbiology · 2020Article
- Enlightening Gliotoxin Biological System in Agriculturally RelevantFrontiers in microbiology · 2020Article
- Mining for Microbial Gems: Integrating Proteomics in the Postgenomic Natural Product Discovery Pipeline.Proteomics · 2018Review
- The Transcription Factor ZafA Regulates the Homeostatic and Adaptive Response to Zinc Starvation inGenes · 2018Article
- Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion.BMC genomics · 2018Article
- Molecular Insights Into Development and Virulence Determinants ofFrontiers in cellular and infection microbiology · 2018Review
- Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles.Microorganisms · 2017Article
- Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, inFrontiers in microbiology · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI. Indirect identification of secondary metabolite cluster expression was also achieved, with proteins (n = 18) from LaeA-regulated clusters detected, including GliT encoded within the gliotoxin biosynthetic cluster. Biochemical analysis then revealed that gliotoxin significantly attenuates H2O2-induced oxidative stress in A. fumigatus (p>0.0001), confirming observations from proteomics data. A complementary 2-D/LC-MS/MS approach further elucidated significantly increased abundance (p<0.05) of proliferating cell nuclear antigen (PCNA), NADH-quinone oxidoreductase and the gliotoxin oxidoreductase GliT, along with significantly attenuated abundance (p<0.05) of a heat shock protein, an oxidative stress protein and an autolysis-associated chitinase, when gliotoxin and H2O2 were present, compared to H2O2 alone. Moreover, gliotoxin exposure significantly reduced the abundance of selected proteins (p<0.05) involved in de novo purine biosynthesis. Significantly elevated abundance (p<0.05) of a key enzyme, xanthine-guanine phosphoribosyl transferase Xpt1, utilised in purine salvage, was observed in the presence of H2O2 and gliotoxin. This work provides new insights into the A. fumigatus proteome and experimental strategies, plus mechanistic data pertaining to gliotoxin functionality in the organism.
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