Biosynthetic Pathways of Secondary Metabolites in Lichens

Lichens are intimate symbioses between a fungal partner (the mycobiont) and a photosynthetic partner (the photobiont), collectively producing a rich array of secondary metabolites. These compounds—polyketides, nonribosomal peptides, terpenes and phenolic depsides and depsidones—serve ecological functions such as ultraviolet protection, antimicrobial defence and regulation of symbiotic interactions. Biosynthesis is orchestrated by modular enzyme assemblies encoded in biosynthetic gene clusters (BGCs), chiefly polyketide synthases (PKSs), nonribosomal peptide synthetases (NRPSs) and terpene synthases. Advances in genome mining, metagenomic sequencing and molecular networking have revealed far more cryptic BGCs than previously appreciated, while strategies such as OSMAC (One Strain Many Compounds) and heterologous expression now enable activation and characterisation of silent pathways. Together with spatial imaging techniques, these developments are transforming our understanding of how pathway architecture, regulatory networks and cellular microenvironments give rise to chemical diversity with pharmaceutical and agrochemical potential.

Research from Nature Portfolio

Recent work has employed laser desorption/ionisation mass spectrometry imaging (LDI-MSI) to map the in situ distribution of specialised metabolites within the thallus of a model lichen species. By visualising compounds such as usnic acid and an unexpectedly localised miriquidic acid, researchers have linked micro-scale chemical patterns to ecological roles in photoprotection and herbivore deterrence. This spatially resolved approach offers a powerful complement to genetic and biochemical studies, illuminating how cellular context influences pathway flux and metabolite accumulation.

Biosynthetic Pathways of Secondary Metabolites in Lichens publication trend

The graph below shows the total number of articles in biosynthetic pathways of secondary metabolites in lichens across all publications each year (not limited to Nature Index journals).

Technical terms

Symbiosis: A close and long-term interaction between two different organisms, such as fungi and algae in lichens.

Polyketide synthase (PKS): A modular enzyme that catalyses the stepwise assembly of polyketide secondary metabolites.

Biosynthetic gene cluster (BGC): A co-localised set of genes that collectively encode the enzymes for a specific secondary metabolite pathway.

OSMAC strategy: ‘One Strain Many Compounds’, an approach to trigger the expression of silent gene clusters under varied culture conditions.

Imaging mass spectrometry: A technique that maps the spatial distribution of metabolites directly on biological samples.

References

1. Discovery and excavation of lichen bioactive natural products. Frontiers in Microbiology (2023).
2. Biosynthetic gene cluster synteny: Orthologous polyketide synthases in Hypogymnia physodes, Hypogymnia tubulosa, and Parmelia sulcata. MicrobiologyOpen (2023).
3. Are there conserved biosynthetic genes in lichens? Genome-wide assessment of terpene biosynthetic genes suggests ubiquitous distribution of the squalene synthase cluster. BMC Genomics (2024).
4. Spatial mapping of lichen specialized metabolites using LDI-MSI: chemical ecology issues for Ophioparma ventosa. Scientific Reports (2016).