ArticleApplied and environmental microbiology2012
Nonribosomal peptide synthetase genes pesL and pes1 are essential for Fumigaclavine C production in Aspergillus fumigatus.
Article in Applied and environmental microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 49 citations in OpenAlex.
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- Quantitative characterization of filamentous fungal promoters on a single-cell resolution to discover cryptic natural products.Science China. Life sciences · 2023Article
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- Presence, Mode of Action, and Application of Pathway Specific Transcription Factors inInternational journal of molecular sciences · 2021Review
- Interspecies Genomic Variation and Transcriptional Activeness of Secondary Metabolism-Related Genes inFrontiers in fungal biology · 2021Article
- Molecular mechanisms in grass-Epichloë interactions: towards endophyte driven farming to improve plant fitness and immunity.World journal of microbiology & biotechnology · 2020Review
- Depsipeptide Aspergillicins Revealed by Chromatin Reader Protein Deletion.ACS chemical biology · 2019Article
- Recent advances in the genome mining ofMedChemComm · 2019Review
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- Environmental pH modulates transcriptomic responses in the fungus Fusarium sp. associated with KSHB Euwallacea sp. near fornicatus.BMC genomics · 2018Article
- Constitutive hyperproduction of sorbicillinoids inBiotechnology for biofuels · 2018Article
- Clavine Alkaloids Gene Clusters ofGenes · 2017Review
- Ergot alkaloids contribute to virulence in an insect model of invasive aspergillosis.Scientific reports · 2017Article
- Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus.Genome biology · 2017Article
- Enhancing Nonribosomal Peptide Biosynthesis in Filamentous Fungi.Methods in molecular biology (Clifton, N.J.) · 2016Article
- RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior.BMC genomics · 2015Article
- Genetic engineering activates biosynthesis of aromatic fumaric acid amides in the human pathogen Aspergillus fumigatus.Applied and environmental microbiology · 2015Article
- Review
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7 authors at 2 institutions in 3 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The identity of metabolites encoded by the majority of nonribosomal peptide synthetases in the opportunistic pathogen, Aspergillus fumigatus, remains outstanding. We found that the nonribosomal peptide (NRP) synthetases PesL and Pes1 were essential for fumigaclavine C biosynthesis, the end product of the complex ergot alkaloid (EA) pathway in A. fumigatus. Deletion of either pesL (ΔpesL) or pes1 (Δpes1) resulted in complete loss of fumigaclavine C biosynthesis, relatively increased production of fumitremorgins such as TR-2, fumitremorgin C and verruculogen, increased sensitivity to H(2)O(2), and increased sensitivity to the antifungals, voriconazole, and amphotericin B. Deletion of pesL resulted in severely reduced virulence in an invertebrate infection model (P < 0.001). These findings indicate that NRP synthesis plays an essential role in mediating the final prenylation step of the EA pathway, despite the apparent absence of NRP synthetases in the proposed EA biosynthetic cluster for A. fumigatus. Liquid chromatography/diode array detection/mass spectrometry analysis also revealed the presence of fumiquinazolines A to F in both A. fumigatus wild-type and ΔpesL strains. This observation suggests that alternative NRP synthetases can also function in fumiquinazoline biosynthesis, since PesL has been shown to mediate fumiquinazoline biosynthesis in vitro. Furthermore, we provide here the first direct link between EA biosynthesis and virulence, in agreement with the observed toxicity associated with EA exposure. Finally, we demonstrate a possible cluster cross-talk phenomenon, a theme which is beginning to emerge in the literature.
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