Several Metarhizium Species Produce Ergot Alkaloids in a Condition-Specific Manner.

Genomic sequence data indicate that certain fungi in the genus have the capacity to produce lysergic acid-derived ergot alkaloids, but accumulation of ergot alkaloids in these fungi has not been demonstrated previously. We assayed several species grown under different conditions for accumulation of ergot alkaloids. Isolates of and accumulated the lysergic acid amides lysergic acid α-hydroxyethyl amide, ergine, and ergonovine on sucrose-yeast extract agar but not on two other tested media. Isolates of six other species did not accumulate ergot alkaloids on sucrose-yeast extract agar. Conidia of lacked detectable ergot alkaloids, and mycelia of this fungus secreted over 80% of their ergot alkaloid yield into the culture medium. Isolates of , , , , and produced high concentrations of ergot alkaloids in infected larvae of the model insect , but larvae infected with , , and lacked detectable ergot alkaloids. Alkaloid concentrations were significantly higher when insects were alive (as opposed to killed by freezing or gas) at the time of inoculation with Roots of corn and beans were inoculated with or and global metabolomic analyses indicated that the inoculated roots were colonized, though no ergot alkaloids were detected. The data demonstrate that several species produce ergot alkaloids of the lysergic acid amide class and that production of ergot alkaloids is tightly regulated and associated with insect colonization. Our discovery of ergot alkaloids in fungi of the genus has agricultural and pharmaceutical implications. Ergot alkaloids produced by other fungi in the family Clavicipitaceae accumulate in forage grasses or grain crops; in this context they are considered toxins, though their presence also may deter or kill insect pests. Our data report ergot alkaloids in species and indicate a close association of ergot alkaloid accumulation with insect colonization. The lack of accumulation of alkaloids in spores of the fungi and in plants colonized by the fungi affirms the safety of using species as biocontrol agents. Ergot alkaloids produced by other fungi have been exploited to produce powerful pharmaceuticals. The class of ergot alkaloids discovered in species (lysergic acid amides) and their secretion into the growth medium make species a potential platform for future studies on ergot alkaloid synthesis and modification.