Abstract
BACKGROUND: Ribosomally synthesized and posttranslationally modified peptides (RiPPs) represent a relatively recent addition to the biosynthetic gene cluster (BGC) repertoire of fungi. These BGCs are primarily involved in toxins production and defense-related functions and resulting metabolites also have a significant therapeutic potential. While only a limited number of fungal RiPPs, primarily from a few model fungi, have been characterized, genome mining approaches show that RiPP BGCs are nearly ubiquitous across the fungal kingdom. However, the RiPP biosynthetic landscape of fungi involved in intricate relationship as symbiosis, such as lichen-forming fungi (LFF), remains unexplored. RESULTS: This study presents the first comprehensive survey of RiPP BGCs across 111 LFF genomes employing an integrative framework that combines genome mining, phylogenetic inference, and gene network reconstruction. We identified 987 RiPP BGCs, constituting approximately 17% of the total biosynthetic diversity in LFF, a proportion significantly higher than previously estimated. Most lichen RiPP BGCs are unique and do not cluster with any known RiPP gene cluster. We found two RiPP BGCs that were shared among the members of the family Parmeliaceae (Lecanoromycetes), with the signature gene homologous to ustiloxin signature enzyme, indicating a putative similarity to fungal mycotoxin-related BGCs. While one of these BGCs, members of Clan R1, contains the accessory genes for dikaritin synthesis (tyrosinase and methyltransferase), the accessory genes of other BGCs, members of Clan R2, have not yet been reported from any characterized fungal RiPP BGC but only from bacteria. Additionally, for lichen RiPP BGCs that do not cluster with any known BGCs in the RiPP network, we unraveled the presence of the conserved HXXHC motif in the signature gene and, based on this we report the widespread distribution of putative dikaritin homologs across Lecanoromycetes. CONCLUSIONS: This study highlights the presence and distribution of RiPP BGCs in Lecanoromycetes and identifies two conserved RiPP clusters putatively homologous to dikaritins (involved in mycotoxin production) within the Lecanoromycete family Parmeliaceae and a general prevalence of putative signature dikaritin genes (not the cluster) in Lecanoromycetes. Our study highlights the widespread presence of putative mycotoxin-related BGCs in lichenized fungi.