Unveiling the biosynthetic potential of lichens: a comparative genomic analysis of secondary metabolite diversity in ascomycetes

Anna Pasinato ¹, Laura Maglione ¹, Garima Singh ²

Department of Biology, University of Padua ¹, Department of Biology, University of Padua; Botanical Garden of Padua ²

Lichens, a symbiotic association between a fungus and one or more photobionts, have been considered a rich source of secondary metabolites, owing to the diverse array of bioactive compounds identified from the fungal partner. However, this assumption has not been systematically tested. Directly comparing the chemical diversity of organisms is challenging when using secreted metabolites as a metric, as metabolite secretion is influenced by spatial and temporal cues as well as life stages. Genome mining for biosynthetic gene clusters (BGCs), however, provides an excellent proxy for assessing the biochemical potential of these organisms. In this study, we analyzed 374 genomes of Ascomycete fungi, comprising 136 lichenized and 238 non-lichenized taxa, to compare their biosynthetic potential. Using the automated pipeline antiSMASH, we identified all biosynthetic gene clusters (BGCs) present in these genomes. To assess whether there was a significant difference in biosynthetic potential between lichenized and non-lichenized fungi, we conducted a pairwise t-test. Additionally, we performed a randomization test with 100 samples, using 10,000 replicates, to further validate the results and account for potential sampling variability. We identified 13,687 BGCs, majorly belonging to four classes: polyketide synthase (PKS), terpene, non-ribosomal peptide synthase (NRPS), ribosomally synthesized and post-translationally modified peptide (RiPP), and hybrid BGCs. We found that that lichenized fungi harbor a higher number of BGCs compared to non-lichenized fungi, with a notable enrichment in PKS gene clusters. To further investigate the relationship between phylogeny and BGC richness, we compared closely related lichenized and non-lichenized fungi within the classes Dothidiomycetes, Eurotiomycetes and Lichinomycetes. In Dothidiomycetes and Eurotiomycetes, lichenized fungi exhibit levels of BGC enrichment comparable to those observed in the largest lichenized fungal class, Lecanoromycetes. Notably, Lichinomycetes display a general reduction in BGCs regardless of lifestyle. This class is characterized by smaller genome sizes, which likely contribute to a significant reduction in their secondary metabolite gene content. We propose that the multispecies complex lifestyle of lichens may have driven the diversification of biosynthetic genes in this group of fungi. This study highlights the influence of both lifestyle and evolutionary lineage on BGC richness and provides compelling evidence positioning lichens as promising candidates for biotechnological exploration of their secondary metabolite potential.

Main author career stage: PhD student

Contribution type: Talk

First choice session: 5. Genetics, genomics, and bioinformatics

Second choice session: 4. Structure, physiology, and development