Bimodular Peptide Synthetase SidE Produces Fumarylalanine in the Human Pathogen Aspergillus fumigatus
ABSTRACTThe filamentous moldAspergillus fumigatuscauses invasive aspergillosis, a potentially life-threatening infectious disease, in humans. ThesidEgene 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-[32P]pyrophosphate exchange assayin vitro, which identified fumarate andl-alanine, respectively, as the preferred substrates. Using full-lengthholo-SidE, fumarylalanine (FA) formation was observedin vitro. Furthermore, FA was identified inA. fumigatusculture supernatants under inducing conditions, unlesssidEwas genetically inactivated. As FA is structurally related to established pharmaceutical products exerting immunomodulatory activity, this work may contribute to our understanding of the virulence ofA. fumigatus.