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An Old Yellow Enzyme Gene Controls the Branch Point between Aspergillus fumigatus and Claviceps purpurea Ergot Alkaloid Pathways

机译:一个旧的黄色酶基因控制烟曲霉和紫癜麦角麦角生物碱途径之间的分支点。

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摘要

Ergot fungi in the genus Claviceps and several related fungal groups in the family Clavicipitaceae produce toxic ergot alkaloids. These fungi produce a variety of ergot alkaloids, including clavines as well as lysergic acid derivatives. Ergot alkaloids are also produced by the distantly related, opportunistic human pathogen Aspergillus fumigatus. However, this fungus produces festuclavine and fumigaclavines A, B, and C, which collectively differ from clavines of clavicipitaceous fungi in saturation of the last assembled of four rings in the ergoline ring structure. The two lineages are hypothesized to share early steps of the ergot alkaloid pathway before diverging at some point after the synthesis of the tricyclic intermediate chanoclavine-I. Disruption of easA, a gene predicted to encode a flavin-dependent oxidoreductase of the old yellow enzyme class, in A. fumigatus led to accumulation of chanoclavine-I and chanoclavine-I-aldehyde. Complementation of the A. fumigatus easA mutant with a wild-type allele from the same fungus restored the wild-type profile of ergot alkaloids. These data demonstrate that the product of A. fumigatus easA is required for incorporation of chanoclavine-I-aldehyde into more-complex ergot alkaloids, presumably by reducing the double bond conjugated to the aldehyde group, thus facilitating ring closure. Augmentation of the A. fumigatus easA mutant with a homologue of easA from Claviceps purpurea resulted in accumulation of ergot alkaloids typical of clavicipitaceous fungi (agroclavine, setoclavine, and its diastereoisomer isosetoclavine). These data indicate that functional differences in the easA-encoded old yellow enzymes of A. fumigatus and C. purpurea result in divergence of their respective ergot alkaloid pathways.
机译:锁骨杆菌属的麦角真菌和锁骨科的几个相关真菌类产生有毒的麦角生物碱。这些真菌会产生多种麦角生物碱,包括麦角藤和麦角酸衍生物。麦角生物碱也由远缘相关的机会性人类病原体烟曲霉产生。但是,这种真菌产生的是Festuclavine和Fumigaclavines A,B和C,它们在总的麦角环结构中由四个环组成的最后一个组装的饱和中不同于锁骨真菌的clavine。据推测,这两个谱系在合成三环中间型Chanoclavine-I后的某个时候在发散之前共享麦角生物碱途径的早期步骤。烟曲霉中easA(一种预期编码旧的黄酶类的黄素依赖性氧化还原酶的基因)的破坏导致了chanoclavine-I和chanoclavine-I-醛的积累。烟曲霉easA突变体与来自同一真菌的野生型等位基因的互补恢复了麦角生物碱的野生型特征。这些数据表明烟曲霉easA的产物是将Chaclaclavine-I-醛掺入到更复杂的麦角生物碱中所必需的,大概是通过减少与醛基结合的双键,从而促进闭环。烟曲霉easA突变体与来自紫薇的easA同源物的扩增导致典型的锁骨真菌(农锁藤,塞古克拉韦及其非对映异构体异锁藤)的麦角生物碱积累。这些数据表明,烟曲霉和紫杉的easA编码旧黄色酶的功能差异导致它们各自的麦角生物碱途径发生分歧。

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