Nickles, G. R. | Search bioRxiv

bioRxiv2024

Variation in Biosynthetic Gene Clusters Among Lifestyles Across Kingdom Fungi

Biosynthetic gene clusters (BGCs) produce secondary metabolites, many of which are involved in trophic interactions and carbon acquisition lifestyles of fungi. As such, BGCs are hypothesized to exhibit evolutionary diversification across those lifestyles. We tested this hypothesis by analyzing predicted BGCs in more than 1000 fungal genomes, and their variation among fungal lineages and across putative fungal lifestyles (trophic modes). Analyses revealed that specific BGC classes, such as PKSI, RiPPs, and terpenes, exhibit significant phylogenetic signals, whereas others, like NRPS and PKS-NRPS Hybrids, do not. BGC abundance was associated with fungal lifestyles: pathotrophs generally had lower BGC abundance, while combined lifestyles such as saprotroph-symbiotrophs had higher BGC abundances. These findings suggest that both phylogenetic history and ecological strategies drive BGC distribution, highlighting their roles in fungal biochemical diversification. Understanding these patterns provides insights into fungal community ecology and the evolutionary processes shaping their biosynthetic potential.

genomics↗

bioRxiv2023

Mining for a New Class of Fungal Natural Products: The Evolution, Diversity, and Distribution of Isocyanide Synthase Biosynthetic Gene Clusters

The products of non-canonical isocyanide synthase (ICS) biosynthetic gene clusters (BGCs) have notable bioactivities that mediate pathogenesis, microbial competition, and metal-homeostasis through metal-associated chemistry. We sought to enable research into this class of compounds by characterizing the biosynthetic potential and evolutionary history of these BGCs across the Fungal Kingdom. We developed the first genome-mining pipeline to identify ICS BGCs, locating 3,800 ICS BGCs in 3,300 genomes. Genes in these clusters share promoter motifs and are maintained in contiguous groupings by natural selection. ICS BGCs are not evenly distributed across fungi, with evidence of gene-family expansions in several Ascomycete families. We show that the ICS dit1/2 gene cluster family (GCF), which was thought to only exist in yeast, is present in [~]30% of all Ascomycetes, including many filamentous fungi. The evolutionary history of the dit GCF is marked by deep divergences and phylogenetic incompatibilities that raise questions about convergent evolution and suggest selection or horizontal gene transfers have shaped the evolution of this cluster in some yeast and dimorphic fungi. Our results create a roadmap for future research into ICS BGCs. We developed a website (www.isocyanides.fungi.wisc.edu) that facilitates the exploration, filtering, and downloading of all identified fungal ICS BGCs and GCFs.

microbiology↗