Fungal Secondary Metabolism in the Light of Animal–Fungus Interactions: From Mechanism to Ecological Function

Abstract

Ergot alkaloids and their derivatives have been traditionally used as therapeutic agents; e.g., in migraine and blood pressure regulation. Their production in submerse culture is a long established biotechnological process. Ergot alkaloids are produced mainly by phytopathogenic species of the Clavicipitaceae, with C. purpurea as the best investigated species concerning the biochemistry of alkaloid biosynthesis and molecular genetics. In recent years, endophytic members of this family (e.g., the genus Epichloe) have also become the focus of interest, and detailed research on the early part of the biosynthetic pathway has been performed in the human opportunistic pathogen Aspergillus fumigatus. Taken together, the different methodical approaches in all these systems have generated a detailed understanding of the biosynthetic pathways leading to the different ergot alkaloids and of the structure and evolution of ergot alkaloid synthesis (EAS) clusters, while the regulatory mechanisms of biosynthesis are not yet fully unraveled. The methodical improvements and the increased understanding of the molecular mechanism of action in mammalian cells have opened possibilities for metabolic design approaches and generation of designer pharmaceuticals.