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 amongst others 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 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.
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 a range of other 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, enhanced industrial processes and environmental sustainability. 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 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 (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 viz:
The polyketide (acetyl-polymalonyl) 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 via 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 uses this pathway to produce their secondary metabolites. Usnic acid has been reported to be efficacious against viral candidates such as Arenoviridae viruses and is being used as a lead compound in the development of potent antiviral agents.
The mevalonate pathway
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, and they usually appear pale or colourless.
The shikimic acid pathway
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.
Anaissie E.J, McGinnis M.R, Pfaller M.A (2009). Clinical Mycology. 2nd ed. Philadelphia, PA: Churchill Livingstone Elsevier. London.
Beck R.W (2000). A chronology of microbiology in historical context. Washington, D.C.: ASM Press.
Black, J.G. (2008). Microbiology: Principles and Explorations (7th ed.). Hoboken, NJ: J. Wiley & Sons.
Brooks G.F., Butel J.S and Morse S.A (2004). Medical Microbiology, 23rd edition. McGraw Hill Publishers. USA.
Brown G.D and Netea M.G (2007). Immunology of Fungal Infections. Springer Publishers, Netherlands.
Calderone R.A and Cihlar R.L (eds). Fungal Pathogenesis: Principles and Clinical Applications. New York: Marcel Dekker; 2002.
Chakrabarti A and Slavin M.A (2011). Endemic fungal infection in the Asia-Pacific region. Med Mycol, 9:337-344.
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.
Chemotherapy of microbial diseases. In: Chabner B.A, Brunton L.L, Knollman B.C, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York, McGraw-Hill; 2011.
Chung K.T, Stevens Jr., S.E and Ferris D.H (1995). A chronology of events and pioneers of microbiology. SIM News, 45(1):3–13.
Germain G. St. and Summerbell R (2010). Identifying Fungi. Second edition. Star Pub Co.
Ghannoum MA, Rice LB (1999). Antifungal agents: Mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev, 12:501–517.
Gillespie S.H and Bamford K.B (2012). Medical Microbiology and Infection at a glance. 4th edition. Wiley-Blackwell Publishers, UK.
Larone D.H (2011). Medically Important Fungi: A Guide to Identification. Fifth edition. American Society of Microbiology Press, USA.
Levinson W (2010). Review of Medical Microbiology and Immunology. Twelfth edition. The McGraw-Hill Companies, 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.
Mahon C. R, Lehman D.C and Manuselis G (2011). Textbook of Diagnostic Microbiology. Fourth edition. Saunders Publishers, USA.