Fumiquinones A and B, Nematicidal Quinones Produced by<i>Aspergillus fumigatus</i>

Hayashi, Asami; Fujioka, Shozo; Nukina, Manabu; Kawano, Tsuyoshi; Shimada, Atsumi; Kimura, Yasuo

doi:10.1271/bbb.70110

Cited by 40 publications

(29 citation statements)

References 23 publications

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“…It is conceivable that the production of pseurotin A could contribute to the survival of A. fumigatus in hypoxic microenvironments in the soil,(70) where it could act against competitors like nematodes and microbes. 40,71,72 A demonstrated moderate cytotoxicity against lung fibroblasts(72) and the capacity to inhibit IgE production(40) indicate a possible role of pseurotin A in the pathogenicity of A. fumigatus in mammals.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

et al. 2011

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The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to hypoxia represents an important virulence attribute for A. fumigatus. Therefore, we aimed at obtaining a comprehensive overview about this process on the proteome level. To ensure highly reproducible growth conditions, an oxygen-controlled, glucose-limited chemostat cultivation was established. Two-dimensional gel electrophoresis analysis of mycelial and mitochondrial proteins as well as two-dimensional Blue Native/SDS-gel separation of mitochondrial membrane proteins led to the identification of 117 proteins with an altered abundance under hypoxic in comparison to normoxic conditions. Hypoxia induced an increased activity of glycolysis, the TCA-cycle, respiration, and amino acid metabolism. Consistently, the cellular contents in heme, iron, copper, and zinc increased. Furthermore, hypoxia induced biosynthesis of the secondary metabolite pseurotin A as demonstrated at proteomic, transcriptional, and metabolite levels. The observed and so far not reported stimulation of the biosynthesis of a secondary metabolite by oxygen depletion may also affect the survival of A. fumigatus in hypoxic niches of the human host. Among the proteins so far not implicated in hypoxia adaptation, an NO-detoxifying flavohemoprotein was one of the most highly up-regulated proteins which indicates a link between hypoxia and the generation of nitrosative stress in A. fumigatus.

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Section: Discussionmentioning

confidence: 99%

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

et al. 2011

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“…Together with its non-acetylated form aszonalenin, it was also identified in various fungal strains, e.g. Aspergillus zonatus (4), Aspergillus fumigatus (5), Aspergillus carneus (6), and Neosartorya fischeri IFM52672 (7). Their stereoisomer epiaszonalenins A ( Fig.…”

Section: From the Philipps-universität Marburg Institut Für Pharmazementioning

confidence: 99%

Acetylaszonalenin Biosynthesis in Neosartorya fischeri

Yin

Grundmann

Cheng

et al. 2009

Journal of Biological Chemistry

153

129

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Based on the structural information of acetylaszonalenin isolated from Neosartorya fischeri, a putative biosynthetic gene cluster was identified in the genome sequence of this fungus by genomic mining. This cluster consists of three genes coding for a putative non-ribosomal peptide synthetase (AnaPS), a prenyltransferase (AnaPT), and an acetyltransferase (AnaAT). The coding sequences of anaPT and anaAT were cloned in pQE70 and pQE60, respectively, and overexpressed in Escherichia coli. The soluble His 6 fusion proteins were purified to near homogeneity and characterized biochemically. The structures of the enzymatic products were elucidated by NMR and mass spectroscopy analysis. AnaPT was found to catalyze the reverse prenylation of (

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“…In keeping with the diverse bioactivity of fungal secondary metabolites, nematocidal properties of pseurotin A have previously been reported [57]. A precedent for the biosynthetic products of A. fumigatus gene clusters to moderate the outcome of host-pathogen interactions has recently been demonstrated, where deletion of the NRP synthetase Pes3 (AFUA_5G12730) significantly increases the virulence of A. fumigatus in wax moth larvae [58].…”

Section: Resultsmentioning

confidence: 71%

A Modified Recombineering Protocol for the Genetic Manipulation of Gene Clusters in Aspergillus fumigatus

et al. 2014

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Genomic analyses of fungal genome structure have revealed the presence of physically-linked groups of genes, termed gene clusters, where collective functionality of encoded gene products serves a common biosynthetic purpose. In multiple fungal pathogens of humans and plants gene clusters have been shown to encode pathways for biosynthesis of secondary metabolites including metabolites required for pathogenicity. In the major mould pathogen of humans Aspergillus fumigatus, multiple clusters of co-ordinately upregulated genes were identified as having heightened transcript abundances, relative to laboratory cultured equivalents, during the early stages of murine infection. The aim of this study was to develop and optimise a methodology for manipulation of gene cluster architecture, thereby providing the means to assess their relevance to fungal pathogenicity. To this end we adapted a recombineering methodology which exploits lambda phage-mediated recombination of DNA in bacteria, for the generation of gene cluster deletion cassettes. By exploiting a pre-existing bacterial artificial chromosome (BAC) library of A. fumigatus genomic clones we were able to implement single or multiple intra-cluster gene replacement events at both subtelomeric and telomere distal chromosomal locations, in both wild type and highly recombinogenic A. fumigatus isolates. We then applied the methodology to address the boundaries of a gene cluster producing a nematocidal secondary metabolite, pseurotin A, and to address the role of this secondary metabolite in insect and mammalian responses to A. fumigatus challenge.

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Fumiquinones A and B, Nematicidal Quinones Produced byAspergillus fumigatus

Cited by 40 publications

References 23 publications

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

Analysis of the Aspergillus fumigatus Proteome Reveals Metabolic Changes and the Activation of the Pseurotin A Biosynthesis Gene Cluster in Response to Hypoxia

Acetylaszonalenin Biosynthesis in Neosartorya fischeri

A Modified Recombineering Protocol for the Genetic Manipulation of Gene Clusters in Aspergillus fumigatus

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