Abstract |
The filamentous mold Aspergillus fumigatus causes invasive aspergillosis, a potentially life-threatening infectious disease, in humans. The sidE gene encodes a bimodular peptide synthetase and was shown previously to be strongly upregulated during initiation of murine lung infection. In this study, we characterized the two adenylation domains of SidE with the ATP-[(32)P] pyrophosphate exchange assay in vitro, which identified fumarate and l-alanine, respectively, as the preferred substrates. Using full-length holo-SidE, fumarylalanine (FA) formation was observed in vitro. Furthermore, FA was identified in A. fumigatus culture supernatants under inducing conditions, unless sidE was genetically inactivated. As FA is structurally related to established pharmaceutical products exerting immunomodulatory activity, this work may contribute to our understanding of the virulence of A. fumigatus.
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Authors | Wieland Steinchen, Gerald Lackner, Sabiha Yasmin, Markus Schrettl, Hans-Martin Dahse, Hubertus Haas, Dirk Hoffmeister |
Journal | Applied and environmental microbiology
(Appl Environ Microbiol)
Vol. 79
Issue 21
Pg. 6670-6
(Nov 2013)
ISSN: 1098-5336 [Electronic] United States |
PMID | 23974138
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fumarates
- Peptide Synthases
- Alanine
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Topics |
- Alanine
(biosynthesis, metabolism)
- Aspergillus fumigatus
(enzymology, pathogenicity)
- Base Sequence
- Blotting, Northern
- Escherichia coli
- Fumarates
(metabolism)
- Genetic Complementation Test
- Molecular Sequence Data
- Peptide Synthases
(genetics, metabolism)
- Phylogeny
- Plasmids
(genetics)
- Sequence Alignment
- Virulence
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