Fungal ergot alkaloids: Metabolic pathways, biological functions, and advances in synthetic reprogramming

Ergot alkaloids (EAs) are a class of secondary metabolites produced by fungi. These compounds are predominantly synthesized by Ascomycota, with variations in types and biosynthetic pathways among different fungal species. The EA synthesis has minimal impact on the normal growth and development of most EA-producing fungi, but serves as a virulence factor that influences the biocontrol functions of entomopathogenic fungi and symbiotic fungi in plants. In the medical field, EAs have been widely used for treating neurological disorders such as Parkinson's disease. However, the biosynthetic pathways of EAs are highly complex and significantly influenced by environmental factors, resulting in low yields from field production or chemical synthesis. To address the global demand for EAs, various strategies have been developed to reprogram the biosynthetic pathways in some chassis strains, aiming to simplify the process and increase EA production. This review summarizes the biosynthetic pathways and regulatory mechanisms of EAs in fungi, their biological functions, and recent advances in strategies for synthetic reprogramming.