Recent advances in research for potential utilization of unexplored lichen metabolites.

Several research studies have shown that lichens are productive organisms for the synthesis of a broad range of secondary metabolites. Lichens are a self-sustainable stable microbial ecosystem comprising an exhabitant fungal partner (mycobiont) and at least one or more photosynthetic partners (photobiont). The successful symbiosis is responsible for their persistence throughout time and allows all the partners (holobionts) to thrive in many extreme habitats, where without the synergistic relationship they would be rare or non-existent. The ability to survive in harsh conditions can be directly correlated with the production of some unique metabolites. Despite the potential applications, these unique metabolites have been underutilised by pharmaceutical and agrochemical industries due to their slow growth, low biomass availability and technical challenges involved in their artificial cultivation. However, recent development of biotechnological tools such as molecular phylogenetics, modern tissue culture techniques, metabolomics and molecular engineering are opening up a new opportunity to exploit these compounds within the lichen holobiome for industrial applications. This review also highlights the recent advances in culturing the symbionts and the computational and molecular genetics approaches of lichen gene regulation recognized for the enhanced production of target metabolites. The recent development of multi-omics novel biodiscovery strategies aided by synthetic biology in order to study the heterologous expressed lichen-derived biosynthetic gene clusters in a cultivatable host offers a promising means for a sustainable supply of specialized metabolites.