An ergot alkaloid biosynthesis gene and clustered hypothetical genes from Aspergillus fumigatus
An ergot alkaloid biosynthesis gene and clustered hypothetical genes from Aspergillus fumigatus
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DOI：
10.1128/aem.71.6.3112-3118.2005
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Panaccione, DG
中科院分区：
文献类型：
--
作者：
Coyle, CM;Panaccione, DG
麦角生物碱是一类吲哚衍生的真菌毒素，具有多种重要的生物活性。烟曲霉（Aspergillus fumigatus）是一种常见的空气传播真菌和机会性人类病原体，与相对遥远的锁骨菌科（Clavicipitaceae）分类群中的几种真菌产生不同的麦角生物碱。这些不同真菌的麦角生物碱共享一个四元麦角碱环，但在侧链的数量、类型和位置上有所不同。在麦角真菌中已知麦角生物碱生产所需的几个基因，这些基因聚集在麦角真菌Claviceps purpurea的基因组中。我们研究了烟曲霉的麦角生物碱是否与锁骨菌的麦角生物碱具有共同的生物合成和遗传来源。在烟曲霉（A. fumigatus）基因组中发现了控制麦角生物碱途径决定步骤的基因dmaW的同源基因。敲除dmaW消除了烟曲霉中所有已知的麦角生物碱，而突变的互补恢复了麦角生物碱的生产。在烟曲霉基因组中，与dmaW聚集在一起的序列与先前提出的编码C. purpurea麦角生物碱途径步骤的5个基因相对应，以及其他序列，其推断的蛋白质产物与它们参与麦角生物碱途径一致。相应的基因在核苷酸序列上具有相似性，但其中一些基因的取向和簇内位置不同。结果表明，烟曲霉和锁尾菌的麦角生物碱合成能力具有共同的起源。
The ergot alkaloids are a family of indole-derived mycotoxins with a variety of significant biological activities. Aspergillus fumigatus, a common airborne fungus and opportunistic human pathogen, and several fungi in the relatively distant taxon Clavicipitaceae (clavicipitaceous fungi) produce different sets of ergot alkaloids. The ergot alkaloids of these divergent fungi share a four-member ergoline ring but differ in the number, type, and position of the side chains. Several genes required for ergot alkaloid production are known in the clavicipitaceous fungi, and these genes are clustered in the genome of the ergot fungus Claviceps purpurea. We investigated whether the ergot alkaloids of A. fumigatus have a common biosynthetic and genetic origin with those of the clavicipitaceous fungi. A homolog of dmaW, the gene controlling the determinant step in the ergot alkaloid pathway of clavicipitaceous fungi, was identified in the A. fumigatus genome. Knockout of dmaW eliminated all known ergot alkaloids from A. fumigatus, and complementation of the mutation restored ergot alkaloid production. Clustered with dmaW in the A. fumigatus genome are sequences corresponding to five genes previously proposed to encode steps in the ergot alkaloid pathway of C. purpurea, as well as additional sequences whose deduced protein products are consistent with their involvement in the ergot alkaloid pathway. The corresponding genes have similarities in their nucleotide sequences, but the orientations and positions within the cluster of several of these genes differ. The data indicate that the ergot alkaloid biosynthetic capabilities in A. fumigatus and the clavicipitaceous fungi had a common origin.