Chemotypic and genotypic diversity in the ergot alkaloid pathway of Aspergillus fumigatus

Mycologia ◽  
2012 ◽  
Vol 104 (4) ◽  
pp. 804-812 ◽  
Author(s):  
S. L. Robinson ◽  
D. G. Panaccione
Keyword(s):  
Aspergillus Fumigatus ◽  
Ergot Alkaloid ◽  
Genotypic Diversity

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

2010 ◽  
Vol 76 (12) ◽  
pp. 3898-3903 ◽  
Author(s):  
Christine M. Coyle ◽  
Johnathan Z. Cheng ◽  
Sarah E. O'Connor ◽  
Daniel G. Panaccione
Keyword(s):  
Aspergillus Fumigatus ◽  
Ergot Alkaloid ◽  
Ergot Alkaloids ◽  
Aldehyde Group ◽  
Ring Structure ◽  
Ring Closure ◽  
Claviceps Purpurea ◽  
Wild Type ◽  
Old Yellow Enzyme ◽  
Clavicipitaceous Fungi

ABSTRACT 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.

scholarly journals Structure of anAspergillus fumigatusold yellow enzyme (EasA) involved in ergot alkaloid biosynthesis

2014 ◽  
Vol 70 (10) ◽  
pp. 1328-1332 ◽  
Author(s):  
Annemarie S. Chilton ◽  
Ashley L. Ellis ◽  
Audrey L. Lamb
Keyword(s):  
Crystal Structure ◽  
Amino Acids ◽  
Aspergillus Fumigatus ◽  
Ergot Alkaloid ◽  
Active Site ◽  
Self Regulation ◽  
Unsaturated Aldehyde ◽  
Asymmetric Unit ◽  
Alkaloid Biosynthesis ◽  
Old Yellow Enzyme

TheAspergillus fumigatusold yellow enzyme (OYE) EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine aldehyde and works in conjunction with festuclavine synthase at the branchpoint for ergot alkaloid pathways. The crystal structure of the FMN-loaded EasA was determined to 1.8 Å resolution. The active-site amino acids of OYE are conserved, supporting a similar mechanism for reduction of the α/β-unsaturated aldehyde. The C-terminal tail of one monomer packs into the active site of a monomer in the next asymmetric unit, which is most likely to be a crystallization artifact and not a mechanism of self-regulation.

scholarly journals An Ergot Alkaloid Biosynthesis Gene and Clustered Hypothetical Genes from Aspergillus fumigatus

2005 ◽  
Vol 71 (6) ◽  
pp. 3112-3118 ◽  
Author(s):  
Christine M. Coyle ◽  
Daniel G. Panaccione
Keyword(s):  
Aspergillus Fumigatus ◽  
Ergot Alkaloid ◽  
Biological Activities ◽  
Ergot Alkaloids ◽  
Alkaloid Production ◽  
Genetic Origin ◽  
Biosynthesis Gene ◽  
Opportunistic Human Pathogen ◽  
Clavicipitaceous Fungi ◽  
Hypothetical Genes

ABSTRACT 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.

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