双模块肽合成酶 SidE 在人类病原体烟曲霉中产生延胡索酰苯丙氨酸。
Bimodular peptide synthetase SidE produces fumarylalanine in the human pathogen Aspergillus fumigatus.
机构信息
Department of Pharmaceutical Biology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität, Jena, Germany.
出版信息
Appl Environ Microbiol. 2013 Nov;79(21):6670-6. doi: 10.1128/AEM.02642-13. Epub 2013 Aug 23.
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.
摘要
烟曲霉的丝状霉菌引起侵袭性曲霉病，这是一种潜在的危及生命的传染病，在人类中。sidE 基因编码一个双模块肽合成酶，之前的研究表明，在启动小鼠肺部感染时，该基因的表达水平显著上调。在这项研究中，我们使用体外 ATP-[（32）P]焦磷酸交换测定法对 SidE 的两个氨酰化结构域进行了表征，分别确定延胡索酸和 l-丙氨酸为其首选底物。使用全长的全酶 holo-SidE，在体外观察到了 FA 的形成。此外，在诱导条件下，在烟曲霉的培养上清液中也检测到了 FA，除非 sidE 被基因灭活。由于 FA 的结构与具有免疫调节活性的已上市药物相似，因此这项工作可能有助于我们理解烟曲霉的毒力。
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