Lichens are not single organisms but symbiotic unions between a fungus, the mycobiont, and a photosynthetic partner, an alga or cyanobacterium, called the photobiont. Taxonomically, lichens are classified by their fungal partner, most of which belong to the phylum Ascomycota, with the class Lecanoromycetes being the largest and most species-rich group. Molecular phylogenetics has revealed that the lichenized lifestyle evolved independently in multiple fungal lineages, meaning lichens are not a single natural group but a symbiotic strategy that arose repeatedly during fungal evolution. They come in three principal growth forms: crustose, which forms tightly attached crusts; foliose, with leaf-like lobes; and fruticose, which are shrubby or hair-like. Finer variations include squamulose, gelatinous, leprose and dimorphic forms, each reflecting adaptations to distinct ecological niches.

The chemical heart of the story lies in lichen secondary metabolism. The fungal partner synthesizes an extraordinary array of compounds through polyketide pathways, depositing them as crystals on the surface of the thallus. Major chemical classes include depsides, polyphenolic compounds linked by ester bonds that show antimicrobial, antioxidant and photoprotective activity; depsidones, their cyclic-ether cousins, which often display stronger antimicrobial, antiviral and cytotoxic effects; dibenzofurans such as the famous usnic acid; anthraquinones; pulvinic acid derivatives; xanthones; and various nitrogen-containing alkaloids. Many of these molecules are found nowhere else in nature, and their ecological roles, shielding the thallus from ultraviolet radiation, deterring herbivores and suppressing microbial competitors, remain only partially understood despite decades of experimental work.

Biosynthetically, lichen metabolites flow from three main routes. The acetyl-malonate pathway is the dominant one, beginning with acetyl-CoA and successive malonyl-CoA condensations that build polyketide chains, which are then cyclized, oxidized, reduced and esterified into compounds such as atranorin, evernic acid, salazinic acid, stictic acid, fumarprotocetraric acid and the dibenzofuran usnic acid. The shikimate pathway, funneling through chorismic acid, yields the pulvinic acid pigments like vulpinic acid and calycin that paint lichens in yellow and orange hues while providing UV screening and antimicrobial defense. The mevalonate pathway produces terpenoids and sterols, including zeorin in Cladonia species, hopane-type terpenes in Ramalina and Parmelia, and ergosterol derivatives in Usnea and Evernia. Genomic studies have revealed that lichen-forming fungi harbor large numbers of silent or cryptic biosynthetic gene clusters, organized into coordinated clusters alongside tailoring enzymes such as cytochrome P450 monooxygenases, O-methyltransferases and glycosyltransferases, hinting that the true metabolic repertoire is far larger than anything observed under natural conditions.

How these compounds actually work is increasingly clear. Usnic acid, atranorin and salazinic acid disrupt bacterial and fungal membrane permeability, causing cytoplasmic leakage, while also interfering with essential microbial enzymes and blocking biofilm formation, a major driver of chronic infection and antibiotic resistance. Phenolic metabolites such as evernic acid and usnic acid neutralize reactive oxygen species and boost endogenous defenses like glutathione and antioxidant enzymes. Anti-inflammatory effects arise from inhibition of cyclooxygenase and lipoxygenase and the suppression of pro-inflammatory cytokine expression. On the cancer front, lichen metabolites trigger apoptosis by collapsing mitochondrial membrane potential, releasing cytochrome c and activating caspases, while also arresting the cell cycle and inhibiting angiogenesis. Depsidones such as stictic and norstictic acid have shown antiviral activity against herpes simplex virus in vitro by interfering with viral polymerases and genome replication.

The antimicrobial pedigree of lichens dates back to Burkholder’s pioneering 1944 report on antibiotic activity, followed by Vartia’s broader evidence. Screening studies since then suggest that more than half of all lichen species tested exhibit antimicrobial effects. Extracts of Ramalina farinacea and over 60 New Zealand species inhibited pathogens including Staphylococcus, Escherichia coli, Pseudomonas and Mycobacterium. Usnea ghattensis extracts suppressed multiple Bacillus species and Staphylococcus aureus, while Serbian lichens such as Cladonia furcata and Parmelia caperata were active against both bacteria and fungi. Notably, recent work indicates that usnic acid derivatives and atranorin analogs show enhanced activity against multidrug-resistant bacteria, including MRSA and Mycobacterium tuberculosis, a finding with obvious relevance as antibiotic resistance escalates worldwide.

Antioxidant and antitumor activities round out the pharmacological portfolio. Antarctic lichens display exceptionally high radical-scavenging capacity, with usnic, sekikaic and salazinic acids from Ramalina species proving effective against oxidative stress, and Usnea ghattensis extracts showing hepatoprotective benefits in models of ethanol-induced liver damage. In oncology, usnic acid exhibits antiproliferative effects across multiple cancer cell lines; pannarin from Psoroma species induced apoptosis in prostate carcinoma and melanoma cells; protolichesterinic acid from Cetraria islandica blocked breast cancer cell lines; and gyrophoric acid from Umbilicaria showed strong cytotoxicity. Diffractaic acid, usnic acid and decarboxystenosporic acid from Usnea diffracta demonstrated antipyretic, analgesic and anti-inflammatory effects, while atranorin, lecanoric acid and physodic acid added immunomodulatory properties to the list.

Beyond medicine, lichen chemistry reaches into the kitchen, the bathroom cabinet and the field. Lichens have been eaten for centuries: roughly 15 edible types are consumed in China, species like Parmotrema tinctorum and Everniastrum cirrhatum serve as food supplements in India and the Middle East, and Cladonia rangiferina and Cetraria islandica were traditionally baked into bread in parts of Europe. Parmelia perlata, known as black stone flower, is a prized spice in Indian biryanis and stews. In cosmetics, pulvinic acid derivatives and usnic acid act as natural UV filters with sun protection factors comparable to some commercial sunscreens, while phenolic extracts from Parmelia, Evernia and Cladonia neutralize the free radicals behind skin aging, and antimicrobial metabolites combat acne-causing Propionibacterium acnes. In agriculture, lichen compounds inhibit seed germination and root growth in weeds such as wild oat and barnyard grass, and larvicidal extracts from numerous species kill Aedes aegypti, Culex quinquefasciatus and Anopheles stephensi mosquitoes, offering ecofriendly alternatives to synthetic pesticides. Industrially, lichens supply natural dyes, including the purple orcein derived from lecanoric acid in Parmotrema tinctorum, and the oak moss and tree moss extracts of Evernia prunastri and Pseudevernia furfuracea remain fixtures of the global perfume industry.

Significant obstacles stand between this promise and commercial reality. Lichens grow extraordinarily slowly, often taking years to decades to form mature thalli, and their complex dual-organism biology makes artificial cultivation technically demanding. Metabolite profiles fluctuate with species, environment and season, complicating standardization, and some compounds show cytotoxicity at higher concentrations, demanding rigorous toxicity profiling before clinical use. The review’s authors see a way forward through microbial fermentation of lichen-associated fungi, heterologous expression of biosynthetic genes, metabolic engineering and synthetic biology, combined with green extraction strategies, high-throughput screening and government-backed entrepreneurial initiatives. If those tools mature, the authors argue, lichens could indeed become the “green gold” of sustainable bio-entrepreneurship, provided that conservation keeps pace with exploitation in biodiversity hotspots like the Himalayas, the Western Ghats and Northeastern India, where roughly 2,500 of the world’s estimated 30,000 lichen species reside.

Subject of Research: Bioactive secondary metabolites produced by lichens and their pharmaceutical, nutraceutical, cosmetic and agricultural applications

Article Title: Lichen metabolites as potential natural products: a review

Article References: Sahoo, B., Pradhan, S., Dash, S., Upreti, D. K., & Rath, B. (2026). Lichen metabolites as potential natural products: a review. Discover Chemistry, 3(1), Article 524. https://doi.org/10.1007/s44371-026-00932-x

Image Credits: AI Generated

DOI: 10.1007/s44371-026-00932-x

Keywords: lichens, secondary metabolites, usnic acid, natural products, antimicrobial, anticancer, antioxidant, polyketides, bioprospecting, symbiosis, cosmetics, biopesticides

The team was interested in two particular lichen secondary metabolites: usnic acid, a yellow pigment famous among natural products chemists, and atranorin, a depside compound common in many lichen thalli. Both have documented biological activities, but the researchers set out with a more nuanced question. If individual compounds can kill bacteria on their own, does the full chemical cocktail found in a crude lichen extract do the job even better? The answer from their experiments appears to be a cautious yes, with evidence suggesting that mixtures of metabolites may act synergistically rather than as isolated single agents.

To get a reliable picture of what was inside each extract, the scientists used high-performance liquid chromatography coupled with a diode array detector, an analytical technique that separates complex mixtures and identifies compounds based on how they absorb ultraviolet light. After extracting the lichen material with a one-to-one mixture of methanol and acetone, they quantified usnic acid and atranorin across all eight species. The concentrations ranged from a modest 0.024 percent up to 1.2 percent for usnic acid, and from 0.018 to 0.46 percent for atranorin. These numbers matter because they allow direct comparison between the chemical composition of each species and its measured biological effect, transforming what could have been a simple screening exercise into a structured structure-activity investigation.

The antimicrobial results are where the study becomes genuinely striking. The researchers tested their extracts against four strains of Staphylococcus aureus, the notorious bacterium responsible for everything from skin infections to life-threatening sepsis and a World Health Organization priority pathogen. Using broth microdilution assays to determine the minimum inhibitory concentration, they found that all eight lichen extracts suppressed bacterial growth at concentrations between 0.1 and 0.35 milligrams per milliliter. That places the crude extracts in the same potency range as gentamicin, a standard clinical antibiotic tested at 0.1 milligrams per milliliter in the same assays. Pure usnic acid was even stronger at 0.02 milligrams per milliliter, but the fact that unfractionated extracts approached clinical-antibiotic territory is remarkable for unmodified natural material.

Crucially, the team went beyond simply asking whether the extracts stopped growth. They determined the minimum bactericidal concentration for each extract, the dose at which bacteria are actually killed rather than merely inhibited. When the ratio of the bactericidal concentration to the inhibitory concentration falls below four, microbiologists classify a substance as genuinely bactericidal. Every extract in the study met that criterion against the staphylococcal strains, meaning these lichen compounds do not just hold bacteria in check but destroy them. The same logic applied to the antifungal experiments, where minimum fungicidal concentration to minimum inhibitory concentration ratios also fell below four against the tested Candida strains.

That antifungal activity, while real, was more modest. Extracts inhibited Candida growth at concentrations between 0.4 and 1.0 milligrams per milliliter, a range the authors characterize as moderate. Candida species are among the most common fungal pathogens of humans, and rising resistance to existing antifungal drugs has made the search for new chemical scaffolds increasingly urgent. While a lichen extract would need considerable development before it could inform any clinical antifungal, the finding that these same extracts carry fungicidal activity alongside potent antibacterial effects makes them chemically richer candidates for follow-up work than many single-purpose natural products.

The study also examined antioxidant capacity, another dimension of lichen chemistry that has attracted attention for its possible health relevance. Using three complementary assays, the researchers measured the ability of the extracts to neutralize synthetic radicals and reduce iron. In the DPPH radical scavenging assay, effective concentrations fell between 1364 and 2461 micrograms per milliliter. The ABTS decolorization assay yielded values from 11.5 to 15.9 milligrams of Trolox equivalents per gram, while the ferric reducing antioxidant power assay produced readings between 169 and 719.79 micromoles of iron equivalents per gram. Total phenolic content, measured with the Folin-Ciocalteu method, ranged from 11.34 to 332.15 micrograms of gallic acid equivalents per gram, a wide spread that highlights just how chemically different these eight co-occurring species can be.

Among the species tested, one stood out in the antioxidant profiling: the extract of Alectoria ochroleuca showed the second-highest total phenolic content and a moderate antioxidant performance across the assays. Phenolic compounds are well-established antioxidants because their molecular structures can donate electrons or hydrogen atoms to neutralize reactive oxygen species, the unstable molecules implicated in cellular damage, aging, and numerous diseases. In lichens, which endure intense ultraviolet radiation and desiccation on exposed mountain surfaces, an arsenal of protective phenolics makes evolutionary sense. Atranorin and usnic acid themselves contribute to this chemical sunscreen and defense system, which is precisely why lichens have become such attractive targets for pharmacological screening.

The authors are careful about interpretation, and appropriately so. Because pure usnic acid outperformed the crude extracts against Staphylococcus aureus, and because the biological effects did not map neatly onto the concentrations of any single measured compound, the data point toward synergy among metabolites. In natural products research, synergy is both an opportunity and a complication. It can mean that combinations of molecules achieve effects no individual component could, potentially through multiple mechanisms of attack that also make resistance harder to develop. But it also means that isolating a single magic molecule may never fully reproduce the activity of the whole extract, complicating standardization and drug development. The study’s conclusion emphasizes that future work isolating individual metabolites and evaluating their bioactivity in vivo will be needed to confirm the pharmacological relevance of these extracts.

What makes this research resonate beyond the laboratory is its setting. Lichens are among the hardiest organisms on the planet, thriving on bare rock, tree bark, and harsh Andean slopes where almost nothing else grows, and their chemical inventories remain astonishingly underexplored. Studies like this one, combining rigorous chromatographic quantification with standardized susceptibility testing and antioxidant assays, provide exactly the kind of reproducible baseline data needed to turn folklore about healing lichens into testable pharmacology. With antibiotic resistance climbing worldwide and the pipeline of new drugs running thin, the humble organisms carpeting a Peruvian mountainside may hold molecular lessons that modern medicine has barely begun to read. The next chapter will depend on whether the synergistic activity seen in these crude extracts survives the journey from the extraction flask through animal studies and, eventually, toward the clinic.

Subject of Research: Antimicrobial and antioxidant activities of eight Peruvian lichen species analyzed by HPLC-DAD quantification of usnic acid and atranorin.

Article Title: HPLC-DAD quantification of usnic acid and atranorin and evaluation of antibacterial and antifungal activities in eight peruvian lichens

Article References: Carrasco, F., Hernández, W., Guerrero, M., Rojas, R., Tamariz-Angeles, C., Olivera-Gonzales, P., Briceño-Luna, V., Solis, E. C., Raposo, C., Rodilla, J. M., & Silva, L. (2026). HPLC-DAD quantification of usnic acid and atranorin and evaluation of antibacterial and antifungal activities in eight peruvian lichens. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05599-6

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05599-6

Keywords: lichens, usnic acid, atranorin, HPLC-DAD, antimicrobial activity, antioxidant, Peru, Staphylococcus aureus, Candida, natural products, secondary metabolites, synergy