Shikimate-malonate pathway

Incorporation experiments proved that lunularin (595) and lunularic acid (598) were biosynthesized by the shikimate-malonate pathway 288, 290). The co-occurrence of (595) and (598), and the presence of a lunularic acid decarboxylase in Lunularia cruciata and Conocephalum conicum indicated that a decarboxylation step was involved in forming naturally occurring C-14 stilbenes and their dihydro products 290, 292). 

Plant metabolism can be separated into primary pathways that are found in all cells and deal with manipulating a uniform group of basic compounds, and secondary pathways that occur in specialized cells and produce a wide variety of unique compounds. The primary pathways deal with the metabolism of carbohydrates, lipids, proteins, and nucleic acids and act through the many-step reactions of glycolysis, the tricarboxylic acid cycle, the pentose phosphate shunt, and lipid, protein, and nucleic acid biosynthesis. In contrast, the secondary metabolites (e.g., terpenes, alkaloids, phenylpropanoids, lignin, flavonoids, coumarins, and related compounds) are produced by the shikimic, malonic, and mevalonic acid pathways, and the methylerythritol phosphate pathway (Fig. 3.1). This chapter concentrates on the synthesis and metabolism of phenolic compounds and on how the activities of these pathways and the compounds produced affect product quality. 

Precursors of phenylpropanoids are synthesized from two basic pathways the shikimic acid pathway and the malonic pathway (see Fig. 3.1). The shikimic acid pathway produces most plant phenolics, whereas the malonic pathway, which is an important source of phenolics in fungi and bacteria, is less significant in higher plants. The shikimate pathway converts simple carbohydrate precursors into the amino acids phenylalanine and tyrosine. The synthesis of an intermediate in this pathway, shikimic acid, is blocked by the broad-spectrum herbicide glyphosate (i.e., Roundup). Because animals do not possess this synthetic pathway, they have no way to synthesize the three aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), which are therefore essential nutrients in animal diets. 

There are diffent pathways by which all phenolic compounds are synthesized [6,7]. The shikimate/arogenate pathway leads, through phenylalanine, to the majority of plant phenolics, and therefore we shall centre the present revision on the detailed description of this pathway. The acetate/malonate pathway leads to some plant quinones but also to various side-chain-elongated phenylpropanoids (e.g. the group of flavonoids). Finally, the acetate/mevalonate pathway leads by dehydrogenation reactions to some aromatic terpenoids. 

Previous researchers have suggested [6,8] that benzophenones are biosynthesized by condensation of metabolites from the shikimate pathway, forming the A-ring, and the acetate-malonate pathway, creating the B-ring. This produces the basic 13-carbon benzophenone skeleton, Fig. (1). Support for this biosynthetic pathway includes the isolation of benzophenone synthase from Centaurium erythraea [9] and research by Atkinson etal. [10] who examined benzophenones as intermediates in the synthesis of xanthones. (Xanthone biosynthesis is reviewed by... 

Many quinones are derived from acetate-malonate pathways (discussed in Chapter 5), some from shikimate pathways (discussed in Chapter 7), and others are derived by oxidative modification of secondary metabolites from a variety of otiher pathways. Quinones of this last type will be discussed with the compounds to which they are biosyntheti-cally related. 

As is true for benzoquinones and anthraquinones, naphthoquinones are derived both by acetate-malonate and by shikimic acid pathways. 

About 150 xanthones have been discovered. Many are po-lyketide derived, although others are formed from combined shikimic acid pathways combined with acetate-malonate units. Three units of malonate react with a hydroxybenzoic acid (Cfi-Ci). Benzophenones may be converted by oxidative ring closure into xanthones (Fig. 10.14) (Weiss and Ed-... 

Chrysophanol (XXIII), an anthraquinone isolated from the leaves of Rumex alpinus (Polygonaceae), is also formed from acetate (and presumably therefore derived via the acetate-malonate pathway) (Leistner and Zenk, 1969) and not, as previously considered, from shikimic acid and mevalonate. Only anthraquinones such as alizarin lacking a C-methyl group and not hy-droxylated in ring A are made in this way, despite an apparent similarity in structure thus at least two independent routes also exist for the synthesis of these compounds and reflect the diversity available for the biogenesis of multiringed phenols in plants. 

Benzenoid compounds in plants are synthesized by two main pathways the shikimic acid pathway and the acetate-malonate pathway. In higher plants, a large number of aromatic compounds are derived from phenylalanine, tyrosine, and tryptophan, end-products of the shikimic acid pathway. 

Thus, the three ansamycins whose biosyntheses have been investigated are derived from closely related biosynthetic pathways. The streptovaricin and rifamycin ansa chains are derived from seven propionate and two acetate (malonate) units, the geldanamycin ansa chain from four propionate, one malonate and two still unidentified 2-carbon units. In two of the three antibiotics (and presumably in streptovaricin as well) a C7N unit is derived from glucose via a shikimate-type pathway. Although a number of late intermediates in the biosynthesis of rifamycin and streptovaricins have been identified, much remains to be done. 

Cinnamic acids, as their coenzyme A esters, may also function as starter units for chain extension with malonyl-CoA units, thus combining elements of the shikimate and acetate pathways (see page 80). Most commonly, three C2 units are added via malonate giving rise to flavonoids and stilbenes, as described in the next section (page 149). However, there are several examples of products formed from a cinnamoyl-CoA starter... 

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