Discovery and excavation of lichen bioactive natural products

Abstract

Lichen natural products are a tremendous source of new bioactive chemical entities for drug discovery. The ability to survive in harsh conditions can be directly correlated with the production of some unique lichen metabolites. Despite the potential applications, these unique metabolites have been underutilized by pharmaceutical and agrochemical industries due to their slow growth, low biomass availability, and technical challenges involved in their artificial cultivation. At the same time, DNA sequence data have revealed that the number of encoded biosynthetic gene clusters in a lichen is much higher than in natural products, and the majority of them are silent or poorly expressed. To meet these challenges, the one strain many compounds (OSMAC) strategy, as a comprehensive and powerful tool, has been developed to stimulate the activation of silent or cryptic biosynthetic gene clusters and exploit interesting lichen compounds for industrial applications. Furthermore, the development of molecular network techniques, modern bioinformatics, and genetic tools is opening up a new opportunity for the mining, modification, and production of lichen metabolites, rather than merely using traditional separation and purification techniques to obtain small amounts of chemical compounds. Heterologous expressed lichen-derived biosynthetic gene clusters in a cultivatable host offer a promising means for a sustainable supply of specialized metabolites. In this review, we summarized the known lichen bioactive metabolites and highlighted the application of OSMAC, molecular network, and genome mining-based strategies in lichen-forming fungi for the discovery of new cryptic lichen compounds.

Discovery and heterologous expression of functional 4-O-dimethylallyl-L-tyrosine synthases from lichen-forming fungi

“…Fungi are proficient producers of secondary metabolites: specialized molecules that are not strictly required for growth or survival, but that play important roles in sexual development, communication and competition with other organisms, and defense from environmental stressors [1]. In particular, lichen-forming fungi—organisms living in symbiotic associations with algae or cyanobacteria in nature—are prolific producers of secondary metabolites, notably bioactive aromatic polyketides and natural dyes [2–5]. Lichens are relatively underexplored because of their complex biology, as well as the technical challenges around cultivation in laboratory settings [6].…”

Genome-Wide Analysis of the Cytochrome P450 Monooxygenases in the Lichenized Fungi of the Class Lecanoromycetes

“…One line of defense is the biosynthesis of secondary metabolites, chemicals produced by an organism that are not required for its growth, development, and reproduction but have biological activity that can indirectly equip the organism to defend better and survive. It is well known that lichens produce a wide range of secondary metabolites, and harnessing their potential for human benefit has received much attention [9][10][11].…”