Pathways shikimic acid

Use of Mutants in Biosynthetic Studies Formation of Chorismic Acid Derivatives of Chorismic Acid Biosynthesis of Tryptophan Indole 3-Acetic Acid Avenalumins from Oats DIMBOA and Related Compounds Biosynthesis of Phenylalanine and Tyrosine Compounds Derived from Shikimic Pathway Intermediates 

Derivatives of wo-Chorismic Acid Arbutin and Hydroquinones References 

Plants and microorganisms are capable of making aromatic amino acids, but most animals cannot. In particular, animals cannot synthesize L-phenylalanine and L-tryptophan and are dependent on bacterial or plant sources of these essential compounds. Many animals can make L-tyrosine from L-phenylalanine. 

Most aromatic compounds in plants are derived from shikimic acid metabolism many of these substances are phenols. Compounds derived from this pathway are extensively modified and considered under other classes of plant secondary metabolites. Although many types of secondary compounds are produced from intermediates of the shikimic acid pathway (e.g., certain naphthoquinones and anthraquinones discussed in Chapter 6), most are derived from four aromatic amino acids phenylalanine, tyrosine, anthranilic acid, and tryptophan. Aromatic compounds that arise from the shikimic acid pathway usually can be distinguished from those of other origins by their substitution patterns and by a knowledge of the compounds with which they co-occur. 

Shikimic acid, for which the pathway is named, was first discovered in the plant Illicium religiosum in 1885 and was named after the Japanese name for the plant, shikimi-no-ki. The compound makes up 20% of the dry weight of the fruits of this plant. For many years, chemists considered this com- 

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E. E. Conn, The Shikimic Acid Pathway, Plenum Press, New York, 1986. 

The earliest references to cinnamic acid, cinnamaldehyde, and cinnamyl alcohol are associated with thek isolation and identification as odor-producing constituents in a variety of botanical extracts. It is now generally accepted that the aromatic amino acid L-phenylalanine [63-91-2] a primary end product of the Shikimic Acid Pathway, is the precursor for the biosynthesis of these phenylpropanoids in higher plants (1,2). 

Phenazines — The phenazines are biosynthesized by the shikimic acid pathway, through the intermediate chorismic acid. The process was studied using different strains of Pseudomonas species, the major producers of phenazines. The best-known phenazine, pyocyanine, seems to be produced from the intermediate phenazine-1-carboxylic acid (PCA). Although intensive biochemical studies were done, not all the details and the intermediates of conversion of chorismic acid to PCA are known. In the first step, PCA is N-methylated by a SAM-dependent methyltransferase. The second step is a hydroxylative decarboxylation catalyzed by a flavoprotein monooxygenase dependent on NADH. PCA is also the precursor of phenazine-1-carboxamide and 1-hydroxyphenazine from Pseudomonas species. - - ... 

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

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. 

Allelopathic compounds consist of a wide variety of chemical types which arise through either the acetate or the shikimic acid pathway (5 ). These compounds range from very simple gases and aliphatic compounds to complex multi-ringed aromatic compounds. Oniy a few examples are mentioned below. 

Phenylalanine Ammonia-Lyase. The building units of lignin are formed from carbohydrate via the shikimic acid pathway to give aromatic amino acids. Once the aromatic amino acids are formed, a key enzyme for the control of lignin precursor synthesis is phenylalanine ammonia-lyase (PAL) (1). This enzyme catalyzes the production of cinnamic acid from phenylalanine. It is very active in those tissues of the plant that become lignified and it is also a central enzyme for the production of other phenylpropanoid-derived compounds such as flavonoids and coumarins, which can occur in many parts of the plant and in many different organs (35). Radioactive phenylalanine and cinnamic acid are directly incorporated into lignin in vascular tissue (36). 

Alkaloid biosynthesis needs the substrate. Substrates are derivatives of the secondary metabolism building blocks the acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid and 1-deoxyxylulose 5-phosphate (Figure 21). The synthesis of alkaloids starts from the acetate, shikimate, mevalonate and deoxyxylulose pathways. The acetyl coenzyme A pathway (acetate pathway) is the source of some alkaloids and their precursors (e.g., piperidine alkaloids or anthraniUc acid as aromatized CoA ester (antraniloyl-CoA)). Shikimic acid is a product of the glycolytic and pentose phosphate pathways, a construction facilitated by parts of phosphoenolpyruvate and erythrose 4-phosphate (Figure 21). The shikimic acid pathway is the source of such alkaloids as quinazoline, quinoline and acridine. 

The plant polyphenols—the phenylpropanoids made via the shikimic acid pathway... 

A large number of volatile phenols and related compounds occur in vegetables and fruits, and some of them are potent aroma compounds. The majority of volatile phenols and related compounds in plants are formed mainly through the shikimic acid pathway, and are present in intact plant tissue either as free... 

Claisen rearrangement plays an important part in the biosynthesis of several natural products. For example, the chorismate ion is rearranged to the prephenate ion by the Claisen rearrangement, which is catalysed by the enzyme chorismate mutase. This prephenate ion is a key intermediate in the shikimic acid pathway for the biosynthesis of phenylalanine, tyrosine and many other biologically important natural products. 

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. 

Coumarins and isocoumarins appear to be of varied origins. Simple coumarins, such as umbelliferone, are formed by the shikimic acid pathway in which hydroxylation of p-hydroxycinnamic acid occurs. Other coumarins, for example alternariol (690), are derived from a polyketide unit, as are a number of chromanones, chromones, pyranones and isocoumarins (B-78MI22400). The biosynthesis of 5-hydroxy-2-methylchromone has been shown to involve the chromanone (60JCS654). However, isocoumarins are also derived from the mixed acetate-shikimate route, through initial cyclization of the polyketide and subsequent lactonization. 

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 3-deoxy D-arabino-heptulosonic acid 7-phosphate (DAHP, 34), intermediate of the shikimic acid pathway (cf. Sect. 2.2.4), has also been prepared... 

Humphreys JL, Lowes DJ, Wesson KA, Whitehead RC (2006) Arene cw-Dihydrodiols -Useful Precursors for the Preparation of Antimetabolites of the Shikimic Acid Pathway Application to the Synthesis of 6,6-Difluoroshikimic Acid and (6S)-6-Fluoroshikimic Acid. Tetrahedron 62 5099... 

Any chemical produced by a plant (donor) that stimulates or inhibits the growth of a neighbour (receiver or receptor) is broadly termed an allelochemical. Typically, allelochemicals are secondary metabolites (Whittaker and Feeney 1971 Rice, 1984 Rizvi et al., 1992), produced as by-products of the acetate and shikimic acid pathways. They may also form as degradation products from the action of microbial enzymes... 

Natural Products Originating from Acetate and Shikimic Acid Pathways... 

In contrast to the rutelines, the melolonthine scarabs generally use terpenoid-and amino acid-derived pheromones (reviewed in Leal, 1999). For example, the female large black chafer, Holotrichia parallela Motschulsky, produces methyl (2.S, 3. Sj - 2 - am ino-3-methy lpcn tanoatc (L-isoleucine methyl ester) as an amino acid-derived sex pheromone (Leal et al., 1992 Leal, 1997). There is no direct evidence that the chafer beetles or any other Coleoptera use the shikimic acid pathway for de novo pheromone biosynthesis, but some scarabs and scolytids (see section 6.6.4.2) may convert amino acids such as tyrosine, phenylalanine, or tryptophan to aromatic pheromone components (Leal, 1997,1999). In another melolonthine species, the female grass grab beetle, Costelytra zealandica (White), the phenol sex pheromone is produced by symbiotic bacteria (Henzell and Lowe, 1970 Hoyt et al. 1971). 

Shikimic acid pathway chemical pathway common in plants, bacteria, and fungi, where aromatic amino acids (e.g., tryptophan, phenylalanine, tyrosine) are synthesized, thereby providing the parent compounds for the synthesis of the phenylpropanoid units in lignins. 

The evidence then is that, for rifamycin and other ansamycins, biosynthesis diverts at a so-far unidentified (but early) compound in the shikimic acid pathway to give 3-amino-5-hydroxybenzoic acid (91) (as its CoA ester). This compound then yields, on the one hand, the mitomycins [e.g. porfiromycin (88)1 and, on the other, the CoA ester of P8/1-OG (92), which then affords diverse metabolites such as rifamycin B (87) and actamycin (86) (cf. ref. 83 for a detailed scheme). 

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