SECONDARY METABOLISM: THE BUILDING BLOCKS AND CONSTRUCTION MECHANISMS
Distinctions between primary and secondary are deﬁned, and the basic building blocks used in the biosynthesis of secondary natural products are introduced. Thechemistry underlying how these building blocks are assembled in nature is described, subdivided according to chemical mechanism, including alkylation reactions, Wagner–Meerwein rearrangements, aldol and Claisen reactions, Schiff base formation and Mannich reactions, transaminations, decarboxylations, oxidation and reduction reactions, phenolic oxidative coupling, and glycosylations.
PRIMARY ANDSECONDARY METABOLISM
All organisms need to transform and interconvert a vast number of organic compounds to enable them to live, grow, and reproduce. They need to provide themselves with energy in the form of ATP, and a supply of building blocks to construct their own tissues. An integrated network of enzymemediated and carefully regulated chemical reactions is used for this purpose,collectively referred to as intermediary metabolism, and the pathways involved are termed metabolic pathways. Some of the crucially important molecules of life are carbohydrates, proteins, fats, and nucleic acids. Apart from fats, these are polymeric materials. Carbohydrates are composed of sugar units, whilst proteins are made up from amino acids, and nucleic acids are based on nucleotides. Organisms varywidely in their capacity to synthesize and transform chemicals. For instance, plants are very efﬁcient at synthesizing organic compounds via photosynthesis from inorganic materials found in the environment, whilst other organisms such as animals and microorganisms rely on obtaining their raw materials in their diet, e.g. by consuming plants. Thus, many of the metabolic pathways are concerned withdegrading materials taken in as food, whilst
others are then required to synthesize specialized molecules from the basic compounds so obtained. Despite the extremely varied characteristics of living organisms, the pathways for generally modifying and synthesizing carbohydrates, proteins, fats, and nucleic acids are found to be essentially the same in all organisms, apart from minor variations.These processes demonstrate the fundamental unity of all living matter, and are collectively described as primary metabolism, with the compounds involved in the pathways being termed primary metabolites. Thus degradation of carbohydrates and sugars generally proceeds via the well characterized pathways known as glycolysis and the Krebs/citric acid/tricarboxylic acid cycle, which release energy fromthe organic compounds by oxidative reactions. Oxidation of fatty acids from fats by the sequence called βoxidation also provides energy. Aerobic organisms are able to optimize these processes by adding on a further process, oxidative phosphorylation. This improves the efﬁciency of oxidation by incorporating a more general process applicable to the oxidation of a wide variety of substrates ratherthan having to provide speciﬁc processes for each individual substrate. Proteins taken in via the diet provide amino acids, but the proportions of each will almost certainly vary from the organism’s requirements. Metabolic pathways are thus available to
interconvert amino acids, or degrade those not required and thus provide a further source of energy. Mostorganisms can synthesize only a proportion of the amino acids they actually require for protein synthesis. Those structures not synthesized, so-called essential amino acids, must be obtained from external sources. In contrast to these primary metabolic pathways, which synthesize, degrade, and generally interconvert compounds commonly encountered in all organisms, there also exists an area of metabolism...