Metabolites 2012.2 306 1.4.Primary and Secondary Metabolites (Natural Products) The biosynthesis and breakdown of proteins,fats,nucleic acids and carbohydrates,which are essential to all living organisms,is known as primary metabolism with the compounds involved in the pathways known as"primary metabolites"[26].The mechanism by which an organism biosynthesizes compounds called 'secondary metabolites'(natural products)is often found to be unique to an organism or is an expression of the individuality of a species and is referred to as "secondary metabolism"26.27].Secondary metabolites are generally not essential for the growth,development or reproduction of an organism and are produced either as a result of the organism adapting to its surrounding environment or are produced to act as a possible defense mechanism against predators to assist in the survival of the organism [26.28].The biosynthesis of secondary metabolites is derived from the fundamental processes of photosynthesis,glycolysis and the Krebs cycle to afford biosynthetic intermediates which,ultimately,results in the formation of secondary metabolites also known as natural products [26].It can be seen that although the number of building blocks are limited the formation of novel secondary metabolites is infinite.The most important building blocks employed in the biosynthesis of secondary metabolites are those derived from the intermediates:Acetyl coenzyme A(acetyl-CoA),shikimic acid,mevalonic acid and 1-deoxyxylulose-5-phosphate.They are involved in countless biosynthetic pathways,involving numerous different mechanisms and reactions (e.g.,alkylation,decarboxylation,aldol,Claisen and Schiff base formation [26]. It is hypothesized that secondary metabolism utilizes amino acids and the acetate and shikimate pathways to produce"shunt metabolites"(intermediates)that have adopted an alternate biosynthetic route.leading to the biosynthesis of secondary metabolites Modifications in the biosynthetic pathways may be due to natural causes (e.g..viruses or environmental changes)or unnatural causes (e.g.,chemical or radiation)in an effort to adapt or provide longevity for the organism [29].It is the unique biosynthesis of these natural products,produced by the countless number of terrestrial and marine organisms,which provides the characteristic chemical structures that possess an array of biological activities. 2.Historically Important Natural Products Traditional medicinal practices have formed the basis of most of the early medicines followed by subsequent clinical.pharmacological and chemical studies [5].Probably the most famous and well known example to date would be the synthesis of the anti-inflammatory agent,acetylsalicyclic acid(1) (aspirin)derived from the natural product,salicin (2)isolated from the bark of the willow tree Salix alba L.[30].Investigation of Papaver somniferum L.(opium poppy)resulted in the isolation of several alkaloids including morphine(3),a commercially important drug,first reported in 1803(Figure 1). It was in the 1870s that crude morphine derived from the plant P.somniferum,was boiled in acetic anhydride to yield diacetylmorphine (heroin)and found to be readily converted to codeine(painkiller). Historically,it is documented that the Sumerians and Ancient Greeks used poppy extracts medicinally whilst the Arabs described opium to be addictive [30].Digitalis purpurea L.(foxglove)had been traced back to Europe in the 10th century but it was not until the 1700s that the active constituent digitoxin()a cardiotonic glycoside was found to enhance cardiac conduction,thereby improving theMetabolites 2012, 2 306 1.4. Primary and Secondary Metabolites (Natural Products) The biosynthesis and breakdown of proteins, fats, nucleic acids and carbohydrates, which are essential to all living organisms, is known as primary metabolism with the compounds involved in the pathways known as “primary metabolites” [26]. The mechanism by which an organism biosynthesizes compounds called ‛secondary metabolites’ (natural products) is often found to be unique to an organism or is an expression of the individuality of a species and is referred to as “secondary metabolism” [26,27]. Secondary metabolites are generally not essential for the growth, development or reproduction of an organism and are produced either as a result of the organism adapting to its surrounding environment or are produced to act as a possible defense mechanism against predators to assist in the survival of the organism [26,28]. The biosynthesis of secondary metabolites is derived from the fundamental processes of photosynthesis, glycolysis and the Krebs cycle to afford biosynthetic intermediates which, ultimately, results in the formation of secondary metabolites also known as natural products [26]. It can be seen that although the number of building blocks are limited, the formation of novel secondary metabolites is infinite. The most important building blocks employed in the biosynthesis of secondary metabolites are those derived from the intermediates: Acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid and 1-deoxyxylulose-5-phosphate. They are involved in countless biosynthetic pathways, involving numerous different mechanisms and reactions (e.g., alkylation, decarboxylation, aldol, Claisen and Schiff base formation [26]. It is hypothesized that secondary metabolism utilizes amino acids and the acetate and shikimate pathways to produce “shunt metabolites” (intermediates) that have adopted an alternate biosynthetic route, leading to the biosynthesis of secondary metabolites [29]. Modifications in the biosynthetic pathways may be due to natural causes (e.g., viruses or environmental changes) or unnatural causes (e.g., chemical or radiation) in an effort to adapt or provide longevity for the organism [29]. It is the unique biosynthesis of these natural products, produced by the countless number of terrestrial and marine organisms, which provides the characteristic chemical structures that possess an array of biological activities. 2. Historically Important Natural Products Traditional medicinal practices have formed the basis of most of the early medicines followed by subsequent clinical, pharmacological and chemical studies [5]. Probably the most famous and well known example to date would be the synthesis of the anti-inflammatory agent, acetylsalicyclic acid (1) (aspirin) derived from the natural product, salicin (2) isolated from the bark of the willow tree Salix alba L. [30]. Investigation of Papaver somniferum L. (opium poppy) resulted in the isolation of several alkaloids including morphine (3), a commercially important drug, first reported in 1803 (Figure 1). It was in the 1870s that crude morphine derived from the plant P. somniferum, was boiled in acetic anhydride to yield diacetylmorphine (heroin) and found to be readily converted to codeine (painkiller). Historically, it is documented that the Sumerians and Ancient Greeks used poppy extracts medicinally, whilst the Arabs described opium to be addictive [30]. Digitalis purpurea L. (foxglove) had been traced back to Europe in the 10th century but it was not until the 1700s that the active constituent digitoxin (4), a cardiotonic glycoside was found to enhance cardiac conduction, thereby improving the