Linking Lichen Metabolites to Genes: Emerging Concepts and Lessons from Molecular Biology and Metagenomics

Lichen secondary metabolites have tremendous pharmaceutical and industrial potential. Although more than 1000 metabolites have been reported from lichens, less than 10 have been linked to the genes coding them. The current biosynthetic research focuses strongly on linking molecules to genes as this is fundamental to adapting the molecule for industrial application. Metagenomic-based gene discovery, which bypasses the challenges associated with culturing an organism, is a promising way forward to link secondary metabolites to genes in non-model, difficult-to-culture organisms. This approach is based on the amalgamation of the knowledge of the evolutionary relationships of the biosynthetic genes, the structure of the target molecule, and the biosynthetic machinery required for its synthesis. So far, metagenomic-based gene discovery is the predominant approach by which lichen metabolites have been linked to their genes. Although the structures of most of the lichen secondary metabolites are well-documented, a comprehensive review of the metabolites linked to their genes, strategies implemented to establish this link, and crucial takeaways from these studies is not available. In this review, I address the following knowledge gaps and, additionally, provide critical insights into the results of these studies, elaborating on the direct and serendipitous lessons that we have learned from them.