Phenylalanine, from chorismate

Figure 30.14 Pathway for the bacterial biosynthesis of phenylalanine from chorismate, involving a Claisen rearrangement.

D. L. Siehl, The Biosynthesis ot Tryptophan, Tyrosine and Phenylalanine from Chorismate. In Plant Amino Acids. Biochemistry and Biotechnology] B. K. Singh, Ed. Marcel Dekker New York, 1999 pp 171-204. 

The further biosynthetic pathway to anthocyanins involves the formation of L-phenylalanine from chorismic acid. L-phenylalanine is then converted to trans-cmrL mic acid through fra 5-elimination of ammonia. In a second step fra 5-cinnamic acid is hydroxylated and activated to yield 4-coumaroyl-CoA. In the next step, 4-coumaroyl-CoA is condensed with 3 molecules of malonyl-CoA to yield naringenin chalcone. naringenin chalcone is rapidly and stereospecifically isomerized to naringenin. 

FIGURE 22-19 Biosynthesis of phenylalanine and tyrosine from chorismate in bacteria and plants. Conversion of chorismate to prephenate is a rare biological example of a Claisen rearrangement. 

In plants and bacteria, phenylalanine and tyrosine are synthesized from chorismate in pathways much less complex than the tryptophan pathway. The common intermediate is prephenate (Fig. 22-19). The final step in both cases is transamination with glutamate. 

From Chorismate to Phenylalanine and Tyrosine 1442.Box 25-B The Cyanogenic Glycosides... 

FIGURE 3.1 The biosynthetic pathway from chorismate to L-phenylalanine in Escherichia coli K12. The mnemonic of the genes involved are shown in parentheses below the enzymes responsible for each step. Compound 1 is L-phenylalanine, 2 is chorisimic acid, 3 is prephenic acid, and 4 is phenylpyruvic acid. 

Figure 14.11 illustrates the syntheses of phenylalanine, tyrosine, and tryptophan from chorismate. (Chorismate is also a precursor in the synthesis of the aromatic rings in the mixed terpenoids, e.g., the tocopherols, the ubiquinones, and plastoquinone.)... 

The Biosynthesis of Phenylalanine, Tyrosine, and Tryptophan from Chorismate. 

Prephenlc Acid, l-Carboxy.4-hydroxy-< -oxo-2.5-cyclohexadiene-1-propanoic acid l-carboxy-4-hydraxy-2,S-cyclohexadiene-l-pyruvic acid, C,0H1 Ot mol wt 226.18. C 53.10%, H 4.46%, O 42.44%. Non-aromatic biosynthetic in -termediate that represents a secondary branch-point in the pathway from chorismic acid to phenylalanine and tyrosine, q.q.y., in many organisms. Isoln from cultures of mutant Escherichia coti B. D. Davis, Science 118, 251 (1953). 

The three aromatic amino acids that are biosynthesized in the shikimic acid pathway have much in common. The many stereochemical events occurring between the condensation of compounds 288a and 289 derived from carbohydrates to the formation of prephenic acid 296 have been extensively reviewed including a recent review by ourselves (82), and so we have summarized the stereochemistry of the biosynthesis in Scheme 79. Prephenic acid 296 leads to phenylalanine 297 and tyrosine 298. The mem-substituted amino acids 299 are derived from chorismate 295, as is tryptophan 302, as shown. 

Phenolic compounds include a wide range of secondary metabolites that are biosynthesised from carbohydrates through the shikimate pathway [14]. This is the biosynthetic route to the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, and only occurs in microorganisms and plants. In the first step, the glycolytic intermediate phosphoenol pyruvate and the pentose phosphate intermediate erythrose-4-phosphate are condensed to 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP), a step catalysed by DAHP synthase. Intermediates of the shikimate pathway are 3-dehydroquinate, shikimate, and chorismate (Fig. 1). Phenylalanine is biosynthesised from chorismate, and from phenylalanine all the phenylpropanoids. Quinate is produced from 3-dehydroquinate and incorporated into chlorogenic and isochlorogenic acids (caffeoyl quinic acids) by combination with caffeic acid. Gallic acid is produced from shikimate. 

The indole moiety of the terpenoid indole alkaloids originates from tryptophan, an aromatic amino acid, which is derived from chorismate via anthranilate. Chorismate is a major branching point in plant primary and secondary metabolism. Here the shikimate pathway (Fig. 6) branches into different pathways (Fig. 7), among others leading to the aromatic amino acids tyrosine, phenylalanine, and tryptophan. 

The largest flux of carbon atoms from chorismate goes into the phenylala-nine/tyrosine pathway, among others leading to lignin and important groups of secondary metabolites such as flavonoids and anthocyanins. The first enzyme in that particular pathway, chorismate mutase (CM, EC 5.4.99.5), catalyzes the conversion of chorismate to prephenate (Fig. 8). Both a cytosolic and a plastidial form have been detected in several plants (e.g., 144-147). The plastidial isoform is inhibited by phenylalanine and tyrosine, and activated by tryptophan the other isoform is not affected by these... 

Fig. 8. From chorismate to phenylalanine and tyrosine. (PDHY = prephenate dehydratase EC 4.2.1.51 PDH = prephenate dehydrogenase EC 1.3.1.13 TAT = tyrosine aminotransferase EC 2.6.1.5 PREPAT = prephanate aminotransferase PTDH = pretyrosine dehydrogenase.)...

Chorismate is an intermediate in the biosynthesis of the aromatic amino acids tryptophan, phenylalanine, and tyrosine. Mammals do not synthesize these amino acids bom chorismate. Instead, they obtain the essential aromatic amino acids tryptophan and phenylalanine from the diet, and they can synthesize tyrosine from phenylalanine. Glyphosate is an effective herbicide because it prevents synthesis of aromatic amino acids in plants. But the compound has no effect on mammals because they have no active pathway for de novo aromatic amino acid synthesis. 

Sprenger, G.A. (2007) From scratch to value engineering Escherichia coli wild type cells to the production of L-phenylalanine and other fine chemicals derived from chorismate. Appl. Microbiol Biotechnol., 75, 739-749. 

Both phenylalanine and tyrosine are derived from chorismic acid, which is itself derived from shikimic acid-3-phosphate through the shikimic acid pathway. In this sequence, chorismic acid is first transformed into prephenic acid by chorismate mutase. If prephenic acid is converted into phenylpyruvic acid by... 

From chorismic acid, four major pathways lead to essential metabolites tryptophan, phenylalanine and tyrosine, p-aminobenzoic acid and the folate group of coenzymes, and the isoprenoid quinones (Fig. 7.2). Numerous secondary compounds in plants and other organisms are formed from products and intermediates of these pathways. 

In both bacteria and plants, two additional amino acids, phenylalanine and tyrosine, are formed from chorismic acid. From chorismate, two separate routes diverge and lead to the amino acids L-phenylalanine and L-tyrosine. However, the pathways in bacteria and plants are distinct and involve different intermediates. Both of these pathways pass through the same intermediate, prephenic acid (26) (Fig. 7.9) (Floss,... 

Chorismic acid is the key branch point intermediate in the biosynthesis of aromatic amino acids in microorganisms and plants (Scheme 1.1a) [1]. In the branch that leads to the production of tyrosine and phenylalanine, chorismate mutase (CM, chorismate-pyruvate mutase, EC 5.4.99.5) is a key enzyme that catalyzes the isomerization of chorismate to prephenate (Scheme 1.1b) with a rate enhancement of about lO -lO -fold. This reaction is one of few pericyclic processes in biology and provides a rare opportunity for understanding how Nature promotes such unusual transformations. The biological importance of the conversion from chorismate to prephenate and the synthetic value of the Claisen rearrangement have led to extensive experimental investigations [2-43]. 

L-Phenylalanine and L-tyrosine are formed from chorismic acid (D 8). Two pathways exist for the biosynthesis of L-tyrosine, the 4-hydroxyphenylpyruvate and the L-pretyrosine (arogenate) route (Fig. 266). Both pathways occur in microorganisms and plants. Higher animals are unable to synthesize L-phenyl-alanine and L-tyrosine de novo, but hydroxylate L-phenylalanine to L-tyrosine. Certain insects, however, contain colonies of bacteria in the fat body synthesizing L-phenylalanine and L-tyrosine, which may be used by their hosts. 

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