Biosynthetic pathways Shikimic acid

Vitamins are classified by their solubiUty characteristics iato fat-soluble and water-soluble groups. The fat-soluble vitamins A, E, and K result from the isoprenoid biosynthetic pathway. Vitamin A is derived by enzymic cleavage of the symmetrical C q beta-carotene, also known as pro-vitamin A. Vitamins E and K result from condensations of phytyldiphosphate (C2q) with aromatic components derived from shikimic acid. Vitamin D results from photochemical ring opening of 7-dehydrocholesterol, itself derived from squalene (C q). 

Figure 1. Biosynthetic pathway for production of shikimic acid pathway-derived phenolic compounds in higher plants.

Deoxy-araWno-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36 The synthesis takes place at room temperature and neutral pH... 

Nature utilizes the shikimate pathway for the biosynthesis of amino acids with aryl side chains. These nonprotein amino acids are often synthesized through intermediates found in the shikimate pathway. In many cases, L-a-amino acids are functionalized at different sites to yield nonprotein amino acids. These modifications include oxidation, hydroxylation, halogenation, methylation, and thiolation. In addition to these modifications, nature also utilizes modified biosynthetic pathways to produce compounds that are structurally more complex. When analyzing the structures of these nonprotein amino acids, one can generally identify the structural similarities to one of the L-a-amino acids with aromatic side chains. 

Specific Control of Phytoalexin Accumulation by "Metabolite Shunting" of Biosynthetic Pathways. Graham and coworkers (personal communication), at the Monsanto Laboratories, St. Louis, have developed techniques to selectively shunt defensive metabolites, particularly of the shikimic acid cycle. Through various techniques, certain compounds are applied to plant aerial or root parts, and these compounds have the property of inducing specific accumulations of secondary metabolites. The directions of these accumulations are under known enzymic control (48), and the regulation of these enzymes is achieved by selecting appropriate inducers. Such inducers seem to provide a novel approach to the control of insects by magnifying the ability of plants to produce and concentrate antiherbivory compounds. 

In higher plants, anthraquinones are biosynthesized either via acylpolyma-lonate (as in the plants of the families Polygonaceae and Rhamnaceae) or via shikimic acid pathways (as in the plants of the families Rubiaceae and Gesneriaceae) as presented in the following biosynthetic schemes. 

The mutants that grew in the presence of shikimic acid evidently had the biosynthetic pathway blocked... 

Isoprenoid structures for carotenoids, phytol, and other terpenes start biosynthetically from acetyl coenzyme A (89) with successive additions giving mevalonate, isopentyl pyrophosphate, geranyl pyrophosphate, farnesyl pyrophosphate (from which squalene and steroids arise), with further build-up to geranyl geranyl pyrophosphate, ultimately to a- and /3-carotenes, lutein, and violaxanthin and related compounds. Aromatic hydrocarbon nuclei are biosynthesized in many instances by the shikimic acid pathway (90). More complex polycyclic aromatic compounds are synthesized by other pathways in which naphthalene dimerization is an important step (91). 

The biosynthesis of flavonoids, stilbenes, hydroxycinnamates, and phenolic acids involves a complex network of routes based principally on the shikimate, phenyl-propanoid, and flavonoid pathways (Figs. 1.35 and 1.36). These biosynthetic pathways constitute a complex biological regulatory network that has evolved in vascular plants during their successful transition on land and that ultimately is essential for their growth, development, and survival [Costa et al., 2003]. 

The shikimate biosynthetic pathway occurs in bacteria, plants, and fungi (including yeasts) and is a major entry into the biosynthesis of primary and secondary metabolites, for example aromatic amino acids, menaquinones, vitamins, and antibiotics [1], Starting from erythrose-4-phosphate (E4P) and phosphoenol-pyruvate... 

Phenylpropanoids have an aromatic ring with a three-carbon substituent. Caffeic acid (308) and eugenol (309) are known examples of this class of compounds. Phenylpropanoids are formed via the shikimic acid biosynthetic pathway via phenylalanine or tyrosine with cinnamic acid as an important intermediate. Phenylpropanoids are a diverse group of secondary plant compounds and include the flavonoids (plant-derived dyes), lignin, coumarins, and many small phenolic molecules. They are known to act as feeding deterrents, contributing bitter or astringent properties to plants such as lemons and tea. 

Scheme 10. Possible biosynthetic routes leading from the shikimic acid pathway to betalains and the coexisting flavonoids (excluding anthocyanins) in betalain-bearing members of the Caryophyl-lales.

Chorismic acid 360 is known to be a key intermediate in the shikimate biosynthetic pathway that bacteria and lower plants use to convert carbohydrates into aromatic compounds. 

Davis concluded that shikimic acid was a common precursor of phenylalanine, tyrosine, tryptophan, p-aminobenzoic acid, p-hydroxybenzoic acid, and an unknown sixth factor, and he next set out to determine other substances lying on the biosynthetic pathway. The various mutants were therefore tested for syntrophism, i.e., for the ability of one mutant to produce a substance necessary for the growth of another mutant. There was thus found a thermolabile substance, X, which was a true precursor of shikimic acid (184). X was isolated from culture filtrates and identified as 5-dehydroshikimic acid (744). Similar experiments revealed a substance, W, which was a true precursor of substance X (187, 193). This also was isolated and shown to be 5-dehydroquinic acid (906). The enzyme, named 5-dehydroquinase, converting dehydroquinic acid to dehydroshikimic acid has been partially purified (606). It is fairly stable, has a high specificity, appears to have no cofactors, and is of wide occurrence in bacteria, algae, yeasts, and plants but, as expected, could not be found in mammalian liver. 

From carbohydrate precursors there is another biosynthetic pathway to shikimic acid and further to gallic acid and tannins. Shikimic acid is the starting material, via chorismic acid (formed by reaction with a second molecule of pyruvic acid) which gives rise to aromatic, i.e. phenolic, amino acids. 

Flavonoids are coloured substances and occur as pigments in plants. The chemical structure is built from an acetate-derived component and a segment from the shikimic acid biosynthetic pathway. Knowledge of the... 

Shikimic acid (64) is the biosynthetic precursor to an array of aromatic compounds, including benzoic and cinnamic acids/ This pathway is utilized by microorganisms and plants, but not by animals, which obtain essential shikimate building blocks like phenylalanine from their diets/ Red algae are known to be a prolific source of halogenated phenolic metabolites derived from shikimic acid, comprising approximately 5% of known algal metabolites/ ... 

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