Lichen secondary metabolites: Synthesis pathways and biological activities



Lichens, which are formed by symbiotic relationship between algae and fungi, synthesize naturally many secondary metabolites with different properties and functions, in response to environmental stress. Although lichen secondary metabolites resemble those of other organisms’ (fungi, plants, etc.), most of them are unique chemical compounds formed only through the association between fungi and algae. The adaptation to environmental conditions and self-preservation of lichens, which grow slowly and can survive even in extreme conditions, are made possible by the secondary metabolites. Although it’s known that lichens for a long time have been used for various purposes, the synthesis mechanism of the secondary metabolites is yet to be determined. The studies continue even today. Basically, the idea of three pathways is developed and the mechanism is revealed partially by trying to explain the acetyl polymalonyl pathway, shikimic acid pathway and mevalonic acid pathway. It is of great importance to understand the purpose of metabolites in lichens and to reveal biosynthesis mechanism exactly to increase the quantity, quality and the utilization areas. These substances formed as a natural product by their metabolism, lichens have much potential utilization in industries including medicine, pharmaceutics, food, perfume and dye. Studies uncover new biological activities of these metabolites, such as antibacterial, antifungal, antiviral and anticancer, and increase their importance every day. In this study, current information on the synthesis pathways of secondary metabolites produced in lichen developmental process and various biological activities shown by lichen species were compiled from a lot of studies in the world and in Turkey from the 1950s to the present.


Lichen, Secondary metabolites, Synthesis pathways, Biological activity.

Full Text:

PDF (Türkçe)


Aalto-Korte K., Lauerma A., Alanko K. 2005. Occupational allergic contact dermatitis from lichens in present-day Finland. Contact Dermatitis, 52(1): 36-8.

Açıkgöz B., Karaltı İ., Ersöz M., Coşkun M.Z., Çobanoğlu G., Sesal C. 2013. Screening of antimicrobial and cytotoxic effects of two Cladonia species. Zeitschrift für Naturforschung, 68c: 191-197.

Agar G., Güllüce M., Alsan A., Bozarı S., Karadayı M., Orhan F. 2010. Mutation preventive and antigenotoxic potential of methanol extracts of two natural lichen. Journal of Medicinal Plants Research, 4(20): 2132-2137.

Ağar G., Aslan A., Kotan Sarıoğlu E., Alpsoy L., Çeker S. 2011. Protective activity of the methanol extract of Usnea longissima against oxidative damage and genotoxicity caused by aflatoxin B1in vitro. Turkish Journal of Medical Sciences, 41(6): 1043-1049.

Ahmadjian V. 1993. The lichen symbiosis. John Wiley & Sons, Inc., New York.

Ahmadjian V., Jacobs J.B. 1985. Artificial reestablishment of lichens. IV. Comparison between natural and synthetic thalli of Usnea strigosa. Lichenologist, 17: 149-165.

Ahti T. 2000. Cladoniaceae. Organization for Flora Neotropica and New York Botanical Garden, Flora Neotropica, Bronx, 78: 1-362.

Armaleo D., Zhang Y., Cheung S. 2008. Light might regulate divergently depside and depsidone accumulation in the lichen Parmotrema hypotropum by affecting thallus temperature and water potential. Mycologia, 100(4): 565–576.

Armaleo D., Sun X., Culberson C. 2011. Insights from the first putative biosynthetic gene cluster for a lichen depside and depsidone. Mycologia, 103(4): 741-754.

Asahina Y., Shibata S. 1954. Chemistry of lichen substances. Japan Society for the Promotion of Science, Tokyo.

Aslan A. 2000. Erzurum ve Artvin Çevresinden Toplanan Dört Liken Türünün Yün Boyama Özellikleri. Herba Medica, 7: 21-24.

Asplund J. 2011. Snails avoid the medulla of Lobaria pulmonaria and L. scrobiculata due to presence of secondary compounds. Fungal Ecology, 4: 356-358.

Atalay F., Halici M.B., Mavi A., Çakır A., Odabaşioğlu F., Kazaz C., Aslan A., Küfrevioğlu Ö.İ. 2011. Antioxidant phenolics from Lobaria pulmonaria L. Hoffm. and Usnea longissima Ach. lichen species. Turkish Journal of Chemistry, 35: 647-661.

Basile A., Rigano D., Loppi S., Di Santi A., Nebbioso A., Sorbo S., Conte B., Paoli L., De Ruberto F., Molinari A.M., Altucci L., Bontempo P. 2015. Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin. International Journal of Molecular Sciences, 16: 7861-7875.

Bayır Y., Odabaşoğlu F., Çakır A., Aslan A., Süleyman H., Halıcı M., Kazaz C. 2006. The inhibition of gastric mucosal lesion, oxidative stres and neutrophil-infiltration in rats by the lichen constituent diffractaic acid. Phytomedicine, 13: 584-590.

Bézivin C., Tomasi S., Lohézic-Le Dévéhat F., Boustie J. 2003. Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine, 10(6-7): 499-503.

Cocchietto M., Skert N., Nimis P.L., Sava G. 2002. A review on usnic acid, an interesting natural compound. Naturwissenschaften, 89: 137-146.

Cos P., Vlietinck A.J., Berghe D.V., Maes L. 2006. Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept’. Journal of Ethnopharmacology, 106: 290-302.

Coskun Z.M., Ersoz M., Acıkgoz B., Karaltı I., Çobanoğlu G., Sesal C. 2015. Anti-proliferative and apoptotic effects of methanolic extracts from different Cladonia species on human breast cancer cells. Folia Biologica (Praha), 61: 97-103.

Culberson C.F., Elix J.A. 1989. Lichen substances. Academic Press, London.

Culberson C.F., LaGreca S., Johnson A., Culberson W.L. 2000. Trivaric acid, a new tridepside in the Ramalina americana chemotype complex (lichenized Ascomycota, Ramalinaceae). Bryologist, 102: 595-601.

Çobanoğlu G. 2005. Likenlerin potansiyel kullanımlarına tarihsel bakış ve Türk tıp tarihinde likenler. Türk Liken Topluluğu Bülteni, 1: 14-16.

Çobanoğlu G. 2015. The use of lichens for biomonitoring of atmospheric pollution-Atmosferik kirliliğin biyolojik izlenmesinde likenlerin kullanımı. Sigma Journal of Engineering and Natural Sciences, 33(4): 591-613.

Çobanoğlu G., Yavuz M. 2003. Tıp tarihinde likenlerle tedavi. Yeni Tıp Tarihi Araştırmaları, 9: 37-90.

Çobanoğlu G., Sesal C., Gökmen B., Çakar S. 2010. Evaluation of the antimicrobial properties of some lichens. South Western Journal of Horticulture, 1(2): 153-158.

Çobanoğlu G., Sesal C., Açıkgöz B., Karaltı I. 2016. Evaluation of antimicrobial activity of the lichens Physcia aipolia, Xanthoria parietina, Usnea florida, Usnea subfloridana and Melanohalea exasperata. Modern Phytomorphology, 10: 21-26.

Çolak S., Geyikoğlu F., Aslan A., Deniz G.Y. 2014. Effects of lichen extracts on haematological parameters of rats with experimental insulin-dependent diabetes mellitus. Toxicology and Industrial Health, 30(10):878-87.

Dayan F., Romagni J.G. 2001. Lichens as a potential source of pesticides. Pesticide Outlook, 12: 229-232.

Deduke C., Timsina B., Piercey-Normore M.D. 2012. Effect of environmental change on secondary metabolite production in lichen-forming fungi. In: Young S., (Ed.) International Perspectives on Global Environmental Change. InTech, pp: 197-230.

Eisenreich W., Knispel N., Beck A. 2011. Advanced methods for the study of the chemistry and the metabolism of lichens. Phytochemistry Reviews, 10: 445-456.

Elix J.A. 1996. Biochemistry and secondary metabolites. In (ed. Nash TH) Lichen Biology. Cambridge University Press, Cambridge. pp: 154-180.

Elo H., Matikainen J., Pelttari E. 2007. Potent activity of the lichen antibiotic (+)-usnic acid against clinical isolates of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Naturwissenschaften, 94: 465-468.

Emmerich R., Giez I., Lange O.L., Proksch P. 1993. Toxicity and antifeedant activity of lichen compounds against the polyphagous herbivorous insect Spodoptera littoralis. Phytochemistry, 33(6): 1389-1394.

Eryılmaz E.I., İnal M.S., Ünal Özakça D. 2013. Effect of UV-C radiation on transcription level of polyketide synthase gene (pksI) and photosystem II D1 protein gene (psbA) in Evernia prunastri. Digital Proceeding of THE ICOEST’2013-Cappadocia. C.Ozdemir, S. Şahinkaya, E. Kalıpcı, M.K. Oden (editors), 18-21 June, Nevsehir, Turkey.

Fazio A.T., Adler M.T., Bertoni M.D., Sepulveda C.S., Damonte E.B., Maier M.S. 2007. Lichen secondary metabolites from the cultured lichen mycobionts of Teloschistes chrysophthalmus and Ramalina celastri and their antiviral activities. Zeitschrift für Naturforschung, 62(7-8): 543-549.

Fernandez-Moriano C., Gomez-Serranillos M.P., Crespo A. 2016. Antioxidant potential of lichen species and their secondary metabolites. A systematic review. Pharmaceutical Biology, 54(1): 1-17.

Francolini I., Norris P., Piozzi A., Donelli G., Stoodley P. 2004. Usnic Acid, a Natural Antimicrobial Agent Able To Inhibit Bacterial Biofilm Formation on Polymer Surfaces. Antimicrobial Agents and Chemotherapy, 48(11): 4360-4365.

Frisvad J.C., Anderson B., Thrane U. 2008. The use of secondary metabolite profiling in chemotaxonomy of filamentous fungi. Mycological Research, 112: 231-240.

Gülçin İ., Oktay M., Küfrevioğlu İ., Aslan A. 2002. Determination of antioxidant activity of lichen Cetraria islandica (L) Ach. Journal of Ethnopharmacology, 79(3): 325-329.

Güvenc A., Küpeli Akkol E., Süntar İ., Keles H., Yıldız S., Çalıs İ. 2012. Biological activities of Pseudevernia furfuracea (L.) Zopf extracts and isolation of the active compounds. Journal of Ethnopharmacology, 144: 726-734.

Hamada N. 1991. Environmental factors affecting the content of usnic acid in the lichen mycobiont of Ramalina siliquosa. Bryologist, 94: 57-59.

Hale M.E. 1990. A synopsis of the lichen genus Xanthoparmelia (Vainio) Hale (Ascomycotina, Parmeliaceae). Smithsonian Contributions to Botany, 74: 1-250.

Huneck S. 1999. The significance of lichens and their metabolites. Die Naturwissenschaften, 86: 559-570.

Huneck S., Yoshimura I. 1996. Identification of lichen substances. Springer, Berlin. 493 p.

Huneck S. 2001. New results on the chemistry of lichen substances. In: W. Herz, H. Falk, G.W. Kirby, R.E. Moore (Eds.), Progress in the Chemistry of Organic Products. Springer, New York. pp: 1-276.

Ingolfsdottir K., 2002. Molecules of Interest - Usnic acid. Phytochemistry, 61: 729-736.

Ingolfsdottir K., Hjalmarsdottir M.A., Sigurdsson A., Gudjonsdottir G.A., Brynjolfsdottir A., Steingrimsson O. 1997. In Vitro Susceptibility of Helicobacter pylori to Protolichesterinic Acid from the Lichen Cetraria islandica. Antimicrobial Agents and Chemotherapy, 215-217.

Kaptaner İğci B. 2013. Likenlerin antimikrobiyal etkileri üzerine Türkiye'de yapılan çalışmalar. Liken Araştırmaları Derneği (LİKAD) Bülteni, 2: 22-25.

Karagöz A., Aslan A. 2005. Antiviral and cytotoxic activity of some lichen extracts. Biologia, 60(3): 281-286.

Kasımoğulları S.Ç., Oran S., Arı F., Ulukaya E., Aztopal N., Sarımahmut M., Öztürk Ş. 2014. Genotoxic, cytotoxic and apoptotic effects of crude extracts Usnea filipendula stirt. in vitro. Turkish Journal of Biology, 38: 940-947.

Kosonic M., Rankovic B. 2011. Lichens as possible sources of antioxidants. Pakistan Journal of Pharmaceutical Sciences, 24(2): 165-170.

Kroken S., Glass N.L., Taylor J.W., Yoder O.C., Turgeon B.G. 2003. Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proceedings of the National Academy of Sciences of the United States of America, 15: 670– 675.

LaGreca S. 1999. A phylogenetic evaluation of the Ramalina americana chemotype complex (lichenized Ascomycota, Ramalinaceae) based on rDNA ITS sequence data. Bryologist, 102: 602-618.

Lawrey J.D. 2009. Chemical defense in lichen symbioses. Chapter 11. In: J. White, M. Torre (Eds.), Diversity of Defensive Mutualisms. Taylor & Francis Group Publishers, pp.167-181.

Leandro L.F., Munari C.C., Sato V.L.F.L, Alves J.M., Oliveira P.F.O., Mastrocola D.F.P., Martins S.P.L., Moraes T.S., Oliveira A.I., Tozatti M.G., Cunha W.R., Tavares D.C. 2013. Assessment of the genotoxicity and antigenotoxicity of (+)-usnic acid in V79 cells and Swiss mice by the micronucleus and comet assays. Mutation Research, 753: 101-106.

Llano G.A. 1950. Economic uses of lichens. Annual Report, Smithsonian Institution, Washington D.C.

Lobakova E.S., Smirnov I.A. 2012. Experimental Lichenology. In: Advances in Applied Biotechnology, Prof. Marian Petre (Ed.). pp: 258-276.

Malhotra S., Subban R., Singh A. 2008. Lichens-role in traditional medicine and drug discovery. The Internet Journal of Alternative Medicine, 5(2).

Manojlovic N.T., Solujic S., Sukdolak S., Milosev M. 2005. Antifungal activity of Rubia tinctorum, Rhamnus frangula and Caloplaca cerina. Fitoterapia, 76(2): 244-6.

Miao V., Coëffet-LeGal M.F., Brown D., Sinnemann S., Donaldson G., Davies J. 2001. Genetic approaches to harvesting lichen products. Trends in Biotechnology, 19: 349-355.

Mitrović T., Stamenković S., Cvetković V., Tošıć S, Stanković M., Radojević I., Stefanović O., Čomić L, Dačić D., Ćurčić M., Marković S. 2011. Antioxidant, Antimicrobial and Antiproliferative Activities of Five Lichen Species. International Journal of Molecular Sciences, 12: 5428-5448.

Molnar K., Farkas E. 2010. Current results on biological activities of lichen secondary metabolites: a review. Zeitschrift für Naturforschung, 65c: 157-173.

Nakajima H., Hara K., Yamamoto Y., Itoh K. 2015. Effects of Cu on the content of chlorophylls and secondary metabolites in the Cu-hyperaccumulator lichen Stereocaulon japonicum. Ecotoxicology and Environmental Safety, 113:477-82.

Nash III TH. 2008. Lichen biology. 2nd ed., Cambridge University Press, Cambridge. 486 p.

Nybakken L., Solhaug K.A., Bilger W., Gauslaa Y. 2004. The lichens Xanthoria elegans and Cetraria islandica maintain a high protection against UV-B radiation in Arctic habitats. Oecologia, 140: 211-216.

Odabaşoğlu F., Aslan A., Çakir A., Süleyman H., Karagöz Y., Halici M., Bayir Y. 2004. Comparison of Antioxidant Activity and Phenolic Content of Three Lichen Species. Phytotherapy Research, 18: 938-941.

Oran S. 2013. Türkiye'de likenlerin antioksidan özelliklerinin belirlenmesi konusunda yapılan çalışmalar. Liken Araştırmaları Derneği (LİKAD) Bülteni, 2: 16-22.

Orange A., James P.W., White F.J. 2001. Microchemical methods for the identification of lichens. British Lichen Society.

Özenoğlu S., Aydoğdu G., Dinçsoy A.B., Taghidizaj A.F., Derici K., Yılmaz E., Aras S., Cansaran-Duman D. 2013. Liken sekonder bileşiklerinin farklı insan kanser hücre tipleri üzerine antikanserojenik etkisi. Türk Hijyen ve Deneysel Biyoloji Dergisi, 70(4): 215-26.

Prateeksha P.B.S., Bajpai R., Jadaun V., Kumar J., Kumar S., Upreti D.K., Singh B.R., Nayaka S., Joshi Y., Singh B.N. 2016. The genus Usnea: a potent phytomedicine with multifarious ethnobotany, phytochemistry and pharmacology. The Royal Society of Chemistry, RSC Adv., 6: 21672-21696.

Rancan F., Rosan S., Boehm K., Fernandez E., Hidalgo M.E., Quihot W., Rubio C., Boehm F., Piazena H., Oltmanns U. 2002. Protection against UVB irradiation by natural filters extracted from lichens. Journal of Photochemistry and Photobiology B, 68(2-3): 133-139.

Ranković, B., Ranković, D., Kosanić, M., Maric, D. 2010. Antioxidant and antimicrobial properties of the lichens Anaptychya ciliaris, Nephroma parile, Ochrolechia tartarea and Parmelia centrifuga. Central European Journal of Biology, 5(5): 649-655.

Ren M.R., Hur J.S., Kim J.Y., Park K.W., Park S.C., Seong C.N., Jeong I.Y., Byun M.W., Lee M.K., Seo K.I. 2009. Anti-proliferative effects of Lethariella zahlbruckneri extracts in human HT-29 human colon cancer cells. Food and Chemical Toxicology, 47: 2157-2162.

Rojas J.L., Díaz-Santos M., Valencia-Islas N.A. 2015. Metabolites with antioxidant and photo-protective properties from Usnea roccellina Motyka, a lichen from Colombian Andes. UK Journal of Pharmaceutical and Biosciences, 3(4): 18-26.

Romagni J.G., Dayan F.E. 2002. Structural diversity of lichen metabolites and their potential use. In: R.J. Upadhyay (Ed.), Advances in Microbial Toxin Research and Its Biotechnological Exploitation. Kluwer Academic / Plenum Publishers, New York, pp: 151-169.

Rundel P.W. 1969. Clinal variation in the production of usnic acid in Cladonia subtenuis along light gradients. Bryologist, 72: 40-44.

Schmeda-Hirschmann G.,Tapia A., Lima B., Pertino M., Sortino M., Zacchino S.,Arias A.R., Feresin G.E. 2008. A new antifungal and antiprotozoal depside from the Andean lichen Protousnea poeppigii. Phytotherapy Research, Mar 22(3): 349-55.

Sepulveda B., Chamy M.C., Piovano M., Areche C. 2013. Lichens: Might be considered as a source of gastroprotective molecules? Journal of the Chilean Chemical Society, 58(2): 1750-1752.

Sesal C. 2014. Liken Sekonder Metabolitlerinin Pseudomonas aeruginosa Antimikrobiyal Peptit Mekanizmasına Etkisinin in siliko ve in vitro Ortamda İncelenmesi”, XXXVI. Türk Mikrobiyoloji Kongresi, 12-16 Kasım 2014, Antalya.

Shukla V., Joshi G.P., Rawat M.S.M. 2010. Lichens as a potential natural source of bioactive compounds: a review. Phytochemistry Reviews, 9: 303-314.

Shukla P., Upreti D.K., Nayaka S., Tiwari P. 2014. Natural Dyes from Himalayan Lichens. Indian Journal of Traditional Knowledge, 13/1: 195-201.

Siddiqi M.R. ve Hawksworth D.L. 1982. Nematodes associated with galls on Cladonia glauca, including two new Species. The Lichenologist, 14: 175-184.

Solhaug K.A., Gauslaa Y. 2004. Photosynthates stimulate the UV-B induced fungal anthraquinone synthesis in the foliose lichen Xanthoria parietina. Plant, Cell, and Environment, 27: 167-176.

Stocker-Wörgötter E. 2008. Metabolic diversity of lichen-forming ascomycetous fungi: culturing, polyketide and shikimate metabolite production, and PKS genes. Natural Product Reports, 25: 188-200.

Süleyman H., Yıldırım D., Aslan A., Göçer F., Gepdıremen A., Güvenalp Z. 2002. An investigation of the antiflammatory effects of an extract from Cladonia rangiformis Hoffm. Biological and Pharmaceutical Bulletin, 25(1): 10-13.

Şen H., Aksoy A., Çobanoğlu G., Selvi S. 2014. Natural dyeing works on some lichens species distributed in Ayvacık (Çanakkale) and İvrindi (Balıkesir/Turkey). Biological Diversity and Conservation, 7/3: 184-189.

Triggiani D., Ceccarelli D., Tiezzi A., Pisani T., Munzi S., Gaggi C., Loppi S. (2009). Antiproliferative Activity of Lichen Extracts on Murine Myeloma Cells. Biologia, 64/1: 59 -62.

Varol M., Tay T., Candan M., Turk A., Koparal A.T. 2015. Evaluation of the sunscreen lichen substances usnic acid and atranorin. Biocell, 39(1): 25-31.

Vatne S., Asplund J., Gauslaa Y. 2011. Contents of carbon based defense compounds in the old forest lichen Lobaria pulmonaria vary along environmental gradients. Fungal Ecology, 4: 350-355.

Vijayan P., Raghu C., Ashok G., Dhanaraj S.A., Suresh B. 2004. Antiviral activity of medicinal plants of Nilgiris. Indian Journal of Medical Research, 120: 24-29.

Yavuz M. 2013. Lichens in the prescriptions of Pliny the Elder. Oltenia, Studii şi comunicări, Ştiinţele Naturii, 29(1): 115-119.

Yavuz M., Çobanoğlu G. 2010. Ethnological uses and etymology of the word Usnea in Ebubekir Razi’s “Liber Almansoris”. The British Lichen Society Bulletin, 106: 3-12.


  • There are currently no refbacks.