Biosynthesis of the Aromatic Amino Acids

Mutants of microorganisms can now be conveniently produced and isolated from parent wild-type strains (for review, see 186). Such mutants are invaluable for the determination of metabolic sequences. If, for example, there occurs a sequence 

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As noted previously in Section 11.10, biological dehydrations are also common and usually occur by an ElcB mechanism on a substrate in which the -OH group is two carbons away from a carbonyl group. An example occurs in the biosynthesis of the aromatic amino acid tyrosine. A base first abstracts a proton from the carbon adjacent to the carbonyl group, and the anion intermediate... 

The shikimate pathway results in the biosynthesis of chorismate, which can subsequently serve as a recursor for the biosynthesis of the aromatic amino acids tryptophan, phenylalanine and tyrosine. The biochemistry of... 

We have described reactions from various different pathways in this chapter so far, but now we are going to look at one complete pathway in detail. It is responsible for the biosynthesis of a large number of compounds, particularly in plants. Most important for us is the biosynthesis of the aromatic amino acids Phe (phenylalanine), Tyr (tyrosine), and Trp (tryptophan). These are essentiar amino acids for humans—we have to have them in our diet as we cannot make them ourselves. We gel them from plants and microorganisms. 

Fig. 2 Metabolic pathways in C. glutamicum for biosynthesis of the aromatic amino acids tryptophan, tyrosine, and phenylalanine (a) and amino acids belonging to the aspartate family including lysine, methionine, threonine, and isoleucine (b). Metabolic regulation by feedback inhibition is indicated by dotted lines...

Microbes and plants synthesize aromatic compounds to meet their needs of aromatic amino acids (L-Phe, L-Tyr and L-Trp) and vitamins. The biosynthesis of these aromatics [69] starts with the aldol reaction of D-erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP), which are both derived from glucose via the central metabolism, into DAHP (see Fig. 8.13). DAHP is subsequently converted, via a number of enzymatic steps, into shikimate (SA) and eventually into chorismate (CHA, see later), which is the common intermediate in the biosynthesis of the aromatic amino acids [70] and vitamins. 

The biosynthetic pathway from SA into L-Phe [69, 70] is shown in Fig. 8.15. The synthesis of chorismate (CHA), the common intermediate in the biosynthesis of the aromatic amino acids, requires an extra equivalent of PEP, which limits the yield of L-Phe from glucose to 0.30 mol mol-1 if PEP is not conserved [91]. The further transformation of CHA into phenylpyruvic acid (PPY) suffers from inhibition by L-Phe and is also subject to transcriptional control [69, 92]. The final step is a reductive amination of PPY into L-Phe with consumption of l-G1u. 

Diagram 1. Common-precursor pathway for biosynthesis of the aromatic amino acids. The asterisk represents unknown intermediates. 

The biosynthesis of shikimate, the direct precursor for chorismate, has been reviewed elsewhere 138-141). The shikimate pathway leading to chorismate is located in the plastids. For the two branches from chorismate leading to the aromatic amino acids, it has been postulated that both occur in a plastidial and a cytosolic form 142). The plastidial form is responsible for the aromatic amino acids for primary metabolism, and the cytosolic one for the biosynthesis of the aromatic amino acids used as precursors in secondary metabolism (for a review, see refs. 141,143). 

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. 

C7H,o05, Mr 174.15. needles, D. 1.6, mp. 178-180°C, [a]g -157° (H2O), pKg4.15 (14.1 °C), soluble in water. S. is a widely distributed component of plants and occurs especially in fruits of the star anise (lllicium anisatum, syn. /. religiosum, Illiciaceae Japanese shi-kimi-no-ki). S. is a key intermediate of the so-called shikimic acid pathway which includes the biosynthesis of the aromatic amino acids phenylalanine, tyrosine, and tryptophan. These, in turn, are precursors of numerous alkaloids, flavonoids, and lignans, as well as 4-amino- and 4-hydroxybenzoic acid, gallic acid, tetrahydrofolic acid, ubiquinones, vitamin K, and nicotinic acid. The synthetic racemate melts at 191-192 °C. 

A bifunctional dehydrogenase fromNeurospora which catalyzes the dehydrogenation of quinate and shikimate, functions in the inducible quinate catabolic pathway (Section IV). The catabolic form of the enzyme is distinguished from the form that occurs in the aggregate which is involved in the biosynthesis of the aromatic amino acids (Ahmed and Giles, 1969). 

The biosynthesis of the aromatic amino acids proceeds via shikimic acid. [56] The starting point is erythrose-4-phosphate, which is produced in the Calvin cycle. The enzyme-catalysed aldol condensation with phosphoenol pyruvate leads to a heptulose, 3-deoxy-(D)-arahino-heptulonic add 7-phosphate. Elimination of phosphate produces an enol, which is converted hy a further aldol condensation into 3-dehydroquinic acid. Elimination of water and reduction then yield shikimic add. 

In microorganisms p-hydroxybenzoic ( ), salicylic ( ) and 2,3-dihydroxybenzoic ( 5) acids are all synthesised via chorismic acid > ° in metabolism which is purposeful in character (Fig. 3). -Hydroxybenzoic acid (2 is thus an intermediate in the biosynthesis of the ubiquinones >and 2,3-dihydroxybenzoyl serine (26), as its cyclic trimer enterochelin, is intimately involved in iron transport in some bacteria. Protocatechuic acid ( ) in contrast is probably formed as a shunt-metabolite in certain mutants of Aerobacter aerogenes which are blocked in the biosynthesis of the aromatic amino acids. 

A compound of unsuspected importance was isolated in 1885 from the fruit of Illicium religiosum. To this compound was given the name shikimic acid, a name derived from shikimi-no-ki which is the Japanese name for the plant. Shikimic acid (5.7), it transpired from the very elegant studies of much later investigators, is a key intermediate in the biosynthesis of the aromatic amino acids, L-phenylalanine, L-tyrosine and L-tryptophan, in plants and micro-organisms (animals cannot carry out de novo synthesis using this pathway). These three aromatic amino acids are individually important precursors for numerous secondary metabolites, and so to some extent are earlier biosynthetic intermediates related to shikimic acid, as the ensuing discussion in this chapter and in Chapters 6 and 7 will show. 

The Shikimate Pathway Biosynthesis of the Aromatic Amino Acids... 

BIOSYNTHESIS OF THE AROMATIC AMINO ACIDS FROM CHORISMATE... 

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