An Old Yellow Enzyme Gene Controls the Branch Point between Aspergillus fumigatus and Claviceps purpurea Ergot Alkaloid Pathways
An Old Yellow Enzyme Gene Controls the Branch Point between Aspergillus fumigatus and Claviceps purpurea Ergot Alkaloid Pathways
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DOI：
10.1128/aem.02914-09
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Panaccione, Daniel G.
中科院分区：
文献类型：
--
作者：
Coyle, Christine M.;Cheng, Johnathan Z.;Panaccione, Daniel G.
麦角菌属的麦角真菌和几个相关的真菌群产生有毒的麦角生物碱。这些真菌产生各种麦角生物碱，包括棒状菌和麦角酸衍生物。麦角生物碱也是由远亲、有机会的人类病原体烟曲霉产生的。然而，这种真菌产生Festuclaine和Fumigacavine A、B和C，它们在麦角林环结构中最后组装的四个环的饱和度上与棒状菌科真菌的棒状菌不同。这两个谱系被假设为共享麦角生物碱途径的早期步骤，然后在合成三环中间体Chanoclavine-I后的某个点上出现分歧。烟曲霉菌中预测编码黄素依赖的氧化还原酶的EASA基因的中断导致了chanoclavine-I和chanoclavine-i-醛的积累。将来自同一真菌的野生型等位基因与烟曲霉变异体互补，恢复了麦角生物碱的野生型特征。这些数据表明，烟曲霉菌EASA的产物是将Chanoclavine-I-醛结合到更复杂的麦角生物碱中所必需的，可能是通过减少与醛基共轭的双键，从而促进环的闭合。烟曲霉EASA突变体与来自红豆杉的EASA的同源物增强，导致棒状菌科真菌典型的麦角生物碱的积累(农棒碱、Setoclavine及其非对映异构体异构体)。这些数据表明，烟曲霉和紫云杉的EASA编码的旧黄酶的功能差异导致了它们各自的麦角生物碱途径的差异。
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.