Discovery of pharmaceutically important ergot alkaloids in three species of the fungal genus Aspergillus

Abigail Jones* and Daniel Panaccione

Division of Plant & Soil Sciences, West Virginia University, Morgantown, WV 26506

Presentation Category: Oral-Science & Technology (Oral Presentation #26)

Student’s Major: Biochemistry

Lysergic acid-derived ergot alkaloids are used to produce pharmaceuticals. The fungi that typically produce them are difficult to grow and manipulate, so we mined genomes of fungi with greater industrial potential for ergot alkaloid synthesis genes. We discovered three species of Aspergillus capable of producing lysergic acid-derived ergot alkaloids. Aspergillus leporis, Aspergillus homomorphus, and Aspergillus hancockii all were fast-growing and able to produce large quantities of ergot alkaloids. A. leporis and A. homomorphus secreted most of the ergot alkaloids into the culture medium, which is beneficial for pharmaceutical purposes. A. leporis infected larvae of the insect Galleria mellonella (which is used as a model for microbial pathogenesis of animals), killed the insect, and sporulated on it after its death. High concentrations of ergot alkaloids accumulated in infected insects. A. leporis possessed previously uncharacterized ergot alkaloid synthesis genes; one, called easT, had sequence properties of a major facilitator transporter. We expressed easT in a strain of Aspergillus fumigatus previously engineered to produce lysergic acid but only at low yields to test if easT would increase production or secretion of ergot alkaloids. The easT-transformed A. fumigatus strain produced more ergot alkaloids than the parent strain but retained most of them in the fungus. Our data show for the first time that Aspergillus species are capable of producing lysergic acid-derived ergot alkaloids and indicate these fungi could be useful for production of these pharmaceutically important compounds. The gene clusters in these fungi also are a source of novel ergot alkaloid synthesis genes.

Funding: National Institute of Health (NIH)

Program/mechanism supporting research/creative efforts: Other, was hired through grant funding.