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Lichen is defined as a symbiotic association of slow-growing microorganisms that is composed mainly of a fungus and cyanobacteria or green algae. All microorganisms carry out two modes of metabolism during their lifetime, and these are mainly primary metabolism and secondary metabolism. Primary metabolism is very indispensable to the survival of all microbial cells as it is during this metabolic activity that important compounds (known as primary metabolites) such as nucleic acids, amino acids, vitamins and enzymes are synthesized, broken down and utilized for the sustenance of the organism. Primary metabolism is very significant to the survival of microorganisms and once inhibited, the organism loses its viability and dies. These metabolic intermediates produced in primary metabolism are mainly synthesized during the logarithmic (exponential) phase of their growth. On the other hand, microbial cells produce other classes or types of metabolic intermediates after their normal development (usually at the stationary stage of growth). These other class of compounds have no implications whatsoever on the growth or sustenance of the organism. These compounds are known as secondary metabolites.


The process by which these other groups of metabolic intermediates are produced is called secondary metabolism; while the compounds produced are known as secondary metabolites. Secondary metabolites are often regarded as microbial by-products and examples include: antibiotics, steroids, enzyme inhibitors, immunomodulating agents, alkaloids, toxins and other range of bioactive and antimicrobial products. A large pool of secondary metabolites of microbial origin have been discovered and harnessed to improve the health and living standards of humanity, animals and even plants in terms of: better medication, better foods, improved crop production, enhanced industrial processes and environmental sustainability. Some secondary metabolites are important lead agents for the discovery and development of novel antimicrobial agents and/or antibiotics used for the treatment of some infectious diseases.

Secondary metabolites unlike primary metabolites have no role whatsoever on the growth and reproduction of a microbial cell. They are therefore the natural products of microorganisms (including the lichens). Many secondary metabolites from microorganisms and other natural sources such as lichens form the lead sources of bioactive compounds for the development of novel drugs and other pharmaceuticals because of their recognized antimicrobial potentials. Lichens exhibit a complex biochemical pathway which gives credence to the vast amount of bioactive compounds that they synthesize.

Over 800 secondary metabolites (known as lichen acids) are known to be synthesized by lichens. These lichen acids are usually insoluble in water, and they serve a variety of functions in the lichen association including protection from other competing or rival organisms in their surrounding environments. Lichen acids are the secondary metabolites produced by lichens, and they possess significant bioactive activities. The production of secondary metabolites by lichens is mediated by three key biochemical/biosynthetic pathways in the lichenized fungi, and these pathways include polyketide pathway, mevalonate pathway and shikimic acid pathway.


The polyketide (acetyl-polymalonyl) pathway make use of acetyl-CoA and malonyl-CoA (both derivatives of coenzyme A) to synthesize lichen acids. The secondary metabolites produced by this pathway include dibenzofurans, depsidones, depsones, depsides, usnic acids, chromones, xanthones, and anthraquinones. Acetyl-polymalonyl biosynthetic pathway is derived from the polymalonyl pathway, and a large group of lichens produce their secondary metabolites through this pathway. This biosynthetic pathway is responsible for the synthesis of most of the secondary metabolites produced by lichens. Usnea species lichens which produces usnic acid with potent antiviral activity use this pathway to produce their secondary metabolites. Usnic acid is known to be efficacious against some viral candidates such as Arenoviridae viruses. Usnic acid is also used as a lead compound in the development of potent antiviral agents.    


The secondary metabolites produced by this pathway include diterpenes, triterpenes, carotenoids, and steroids. Mevalonate biosynthetic pathway is also used by other organisms aside lichens to produce secondary metabolites. It produces more secondary metabolites than the shikimic acid pathway. The mevalonate biosynthetic pathway is derived from the acetyl-CoA of the glycolytic pathway. Heterodermia species lichens use this pathway for the synthesis of its secondary metabolites.   


Shikimic acid pathway is a biochemical pathway that plays significant role in the metabolism of carbohydrates and aromatic amino acids. Lichens make use of this pathway for the synthesis of some of its secondary metabolites. Pulvinic acid and terphenylquinones are the secondary metabolites produced by this pathway. Shikimic biosynthetic pathway is derived from the pentose phosphate cycle and amino-acid biosynthesis. This biosynthetic pathway which is only unique to lichens produces only a small group of lichen secondary metabolites including pulvinic acid derivatives which often appear as bright yellow pigments. The Acarospora species and Candelariella species lichens makes use of this pathway to produce their secondary metabolites. Majority of the secondary metabolites produced by lichens are produced by the polyketide biosynthetic pathway (acetyl-polymalonyl) with only few of these metabolic intermediates produced by the mevalonate and shikimic pathway respectively.



Lichens produce two types of metabolites as aforesaid: primary metabolites (for example, carbohydrates and amino acids) and secondary metabolites (for example, alkaloids and lichen acids). Primary metabolites (which are intracellularly secreted) are critical to the survival of the lichens while secondary metabolites are rarely involved in the metabolism or growth of the lichenized fungi. Secondary metabolites of lichens are generally called lichen acids, and they are usually deposited on the surface of the lichen hyphae. Thus, secondary metabolites of lichens are extracellular secretions of lichenized fungi, and they are primarily produced by the mycobiont (i.e., the fungi partner) of the lichen formation.

Lichen acids exhibit numerous amounts of biological and non-biological activities; and these have been exploited by mankind to solve many health related and non-health problems. The secondary metabolites produced by lichens (which are numerous) are unique, and they are rarely sourced from other natural sources. It is noteworthy that lichens only produce secondary metabolites when a suitable fungus is in association with a functional and compatible cyanobacterium and/or green algae. Thus, a suitable fungal partner and an appropriate phycobiont are essential for the secretion of biologically active compounds of lichens.

Some of the biological functions or activities of lichen secondary metabolites are elucidated in this section.

  1. Lichen acids protect the cyanobacteria (phycobiont) from drying.
  2. They serve as anti-herbivores, thus preventing herbivorous animals from feeding on them.
  3. They protect the lichenized formation from possible microbial assault.
  4. They are used in the systematic and phylogeny of lichen classification. 
  5. Lichen acids are used as lead compounds in drug development.
  6. They are used in the formulation of dyes, perfumes and even food.
  7. Lichen secondary metabolites possess anti-tumor, antiviral and cytotoxic activities.
  8. They help make the lichenized association to be pollution tolerant.
  9. Lichen secondary metabolites are used for the development of antibiotics, analgesics, anti-pyretics, and antioxidants.

Further reading

Anaissie E.J, McGinnis M.R, Pfaller M.A (2009). Clinical Mycology. 2nd ed. Philadelphia, PA: Churchill Livingstone Elsevier. London.

Baumgardner D.J (2012). Soil-related bacterial and fungal infections. J Am Board Fam Med, 25:734-744.

Calderone R.A and Cihlar R.L (eds). Fungal Pathogenesis: Principles and Clinical Applications. New York: Marcel Dekker; 2002.

Damian C. Odimegwu, Kenneth Ngwoke, Chika Ejikeugwu and Charles O. Esimone (2015). Lichen Secondary Metabolites as Possible Antiviral Agents. In: Lichen Secondary Metabolites: Bioactive Properties and Pharmaceutical Potential. A Branislav Ranković (Ed). Springer International Publishing, Switzerland. DOI: 10.1007/978-3-319-13374-4_7. PRINT ISBN: 978-3-319-           13373-7, Online ISBN: 978-3-319-13374-4. Pp. 165-177. Available from:

Champoux J.J, Neidhardt F.C, Drew W.L and Plorde J.J (2004). Sherris Medical Microbiology: An

Introduction to Infectious Diseases. 4th edition. McGraw Hill Companies Inc, USA.       

Gladwin M and Trattler B (2006). Clinical Microbiology Made Ridiculously Simple. 3rd edition. MedMaster, Inc., Miami, USA.

Larone D.H (2011). Medically Important Fungi: A Guide to Identification. Fifth edition. American Society of Microbiology Press, USA.

Madigan M.T., Martinko J.M., Dunlap P.V and Clark D.P (2009). Brock Biology of Microorganisms, 12th edition. Pearson Benjamin Cummings Inc, USA.

Stephenson S.L (2010). The Kingdom Fungi: The Biology of Mushrooms, Molds and Lichens. First edition. Timber Press.

Sullivan D.J and Moran G.P (2014). Human Pathogenic Fungi: Molecular Biology and Pathogenic Mechanisms. Second edition. American Society of Microbiology Press, USA.

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