The evolution of secondary metabolism regulation and pathways in the Aspergillus genus

Abstract

Filamentous fungi produce a diverse array of secondary metabolites (SMs) that play ecological roles in defense, virulence, and inter- and intra-species communication. Fungal SMs have both deleterious and beneficial impacts on human health; some are carcinogenic toxins found in contaminated food supplies, while others, such as lovastatin and penicillin, have been repurposed as successful therapeutics. SMs are narrowly taxonomically distributed and highly diverse between species, and the biosynthetic genes and pathways that produce them are among the most fast-evolving in filamentous fungal genomes. SM production is triggered by both biotic and abiotic factors and is controlled by widely conserved transcriptional regulators. To understand how these master transcriptional regulators influence SM production and impact fungal lifestyle, I examined the genome-wide regulatory role of several master SM regulators in different species of the filamentous fungal genus Aspergillus, in different environmental conditions, and during different developmental stages. To further gain insight into the evolution of SM pathways, I leveraged population genomics in the human pathogen Aspergillus fumigatus to determine the drivers of SM genetic diversity. The findings presented here indicate that master SM regulators undergo extensive transcriptional rewiring, interact with multiple abiotic signals, and coordinate with developmental regulators to control SM production, and that novel SMs evolve through extensive genomic reorganization and through incorporation of foreign DNA.