Identification of a Gene Involved in Production of Pharmaceutically Important Lysergic Acid Amides

Kelcie N. Britton*, Chey R. Steen, Jessi K. Sampson, and Daniel G. Panaccione
Division of Plant and Soil Sciences, West Virginia University, Morgantown, WV 26506

Presentation No.: 8

Assigned Category (Presentation Format): Biological & Health Sciences (Oral Presentations)

Student’s Major: Immunology and Medical Microbiology

Ergot alkaloids are lysergic acid containing compounds produced by fungi associated with human and animal toxicoses. Despite their toxicity, modified and appropriately dosed ergot alkaloid derivatives are effective pharmaceutical treatments for some neurodegenerative diseases. Pathways to some ergot alkaloids have been determined, but the final step in synthesis of lysergic acid amides remains elusive. This gap is significant because many of the pharmaceutically relevant ergot alkaloids are derived from lysergic acid amides. Lysergic acid ⍺-hydroxyethylamide (LAH) is the main ergot alkaloid produced by the fungus Metarhizium brunneum. We hypothesize two genes, easP and estA, encode esterases involved in the final step of LAH biosynthesis. To test this hypothesis, CRISPR mutants were engineered in M. brunneum with easP alone or both estA and easP mutated. Analysis of our mutant strains demonstrated the product of easP has a significant role in production of LAH; the easP mutant only accumulated half the LAH measured in non-mutant strains. Mutation of estA did not affect accumulation of lysergic acid amides, indicating the fungus has an alternate path to LAH.

Funding: Arnold and Mabel Beckman Foundation, NIH

Program/mechanism supporting research/creative efforts: the WVU Beckman Scholars Program (Michelle Richards-Babb)