Amino acids biosynthesis of aromatic

The aromatic amino acids, phenylalanine, tryptophan, and tyrosine, are all made from a common intermediate chorismic acid. Chorismic acid is made by the condensation of erythrose-4-phosphate and phosphoenol pyruvate, followed by dephosphorylation and ring closure, dehydration and reduction to give shikimic acid. Shikimic acid is phosphorylated by ATP and condenses with another phosphoenol pyruvate and is then dephosphorylated to give chorismic acid. 

The condensation of phospho-shikimic acid with phosphoenol pyruvate is catalyzed by the enzyme 3-enoylpyruvoylhikimate-5-phosphate synthase, or EPSP synthase for short. This reaction is specifically inhibited by the herbicide glyphosate. 

Glyphosate is toxic to plants and free-living microorganisms because it inhibits aromatic amino acid biosynthesis. On the other hand, it is extremely nontoxic to humans and animals because humans derive their amino acids from the diet. Additionally, it is broken down in the soil, so it is non-persistent. The only problem with glyphosate herbicides is that they will kill crop plants as readily as weeds. Recently, genetically engineered crop varieties have been introduced which are resistant to the herbicide, allowing weeds to be killed preferentially. 

Once chorismate is produced, it can be converted to either tryptophan, tyrosine, or phenylalanine by distinct pathways. Additionally, 

---

Glyphosate kills plants by specifically inhibiting one critical plant enzyme used in the biosynthesis of aromatic amino acids. As such, glyphosate was one of the first commercially successful herbicides to have a primary identified enzyme site of action in plants (4,5). 

The Shikimate pathway is responsible for biosynthesis of aromatic amino acids in bacteria, fungi and plants [28], and the absence of this pathway in mammals makes it an interesting target for designing novel antibiotics, fungicides and herbicides. After the production of chorismate the pathway branches and, via specific internal pathways, the chorismate intermediate is converted to the three aromatic amino acids, in addition to a number of other aromatic compounds [29], The enzyme chorismate mutase (CM) is a key enzyme responsible for the Claisen rearrangement of chorismate to prephenate (Scheme 1-1), the first step in the branch that ultimately leads to production of tyrosine and phenylalanine. 

Schultz and coworkers (Jackson et a ., 1988) have generated an antibody which exhibits behaviour similar to the enzyme chorismate mutase. The enzyme catalyses the conversion of chorismate [49] to prephenate [50] as part of the shikimate pathway for the biosynthesis of aromatic amino acids in plants and micro-organisms (Haslam, 1974 Dixon and Webb, 1979). It is unusual for an enzyme in that it does not seem to employ acid-base chemistry, nucleophilic or electrophilic catalysis, metal ions, or redox chemistry. Rather, it binds the substrate and forces it into the appropriate conformation for reaction and stabilizes the transition state, without using distinct catalytic groups. 

Accordingly, a strain of E. coli was first engineered to produce elevated levels of DHQ by increasing the levels of certain key enzymes transketolase, 3-deoxy-D-arabino-heptulosonic acid 7-phospate (DAHP) synthase, and DHQ synthase. Also, the strain has reduced levels of DHQ dehydratase, which if present would divert some of the metabolic flow into the biosynthesis of aromatic amino acids its blockage results in higher production of quinic acid. 

Fig. 3.3. Shikimate pathwayforthe biosynthesis of aromatic amino acids in plants and lower organisms. The [3,3]-sigmatropic rearrangement of chorismate into prephenate is shown in the box. PEP, phosphoenolpyruvate.

Biosynthesis. Full details of the isolation and characterization of intermediates in the biosynthesis of ubiquinone-8 (233) in E. coli have been described. Two review articles deal with the compartmentation of the biosynthesis of aromatic amino-acids and prenylquinones in higher plants and the regulation of prenylquinone biosynthesis by tyrosine. ... 

Shikimate and Chorismate Are Intermediates in the Biosynthesis of Aromatic Amino Acids... 

Thin layer chromatographic analysis is also highly applicable to the determination of aromatic organic acids.In human organisms, aromatic acids are synthesized as metabolites in intoxication by toluene, xylene, and ethyl benzene. These compounds are easily absorbed through the skin or respiratory system, and are oxidized to aromatic acids. The separation, identification, and quantitative analyses of aromatic acids are also necessary because they appear as semiproducts of the biosynthesis of aromatic amino acids in plants (phenolic acids), and metabolites of numerous toxic substances, drugs, and catecholamines. Polar adsorbents and polar-... 

Figure 7 Biosynthesis of aromatic amino acids and products derived from phenylalanine or from intermediates of the shikimate pathway. Biosynthetically equivalent positions are indicated by colored bars. The atoms indicated by the blue bars are equivalent to atoms from phosphoenol pyruvate precursor followed by the loss of one carbon atom by decarboxylation.

Phosphonomycin,—Yet another synthesis of phosphonomycin (22) has appeared (Scheme 6). The phosphonoaldehyde (23) was treated with pentan-3-one and cyclohexylamine to give (24), which was then converted into its oxime. Tosylation of this oxime followed by treatment with bicarbonate caused the molecule to fragment, liberating the dimethyl ester of (22). Disodium phosphonoacetic acid when administered orally or topically to mice infected with Herpes simplex virus will reduce significantly the mortality of mice caused by this virus. JV-Phosphonomethyl-glycine is a promising herbicide. Recent work has shown that it exerts its effect by inhibiting the biosynthesis of aromatic amino-acids. ... 

Fig. 14.1-4)[411. This compound is an important intermediate in the shikimate pathway for the biosynthesis of aromatic amino acids in plants. The RAMA reaction produced the desired d-threo stereochemistry, and chemical reduction of the keto group gave the desired (6R)-stereoisomer in 60% diastereomeric excess. Other analogs of DAHP are also potentially available by this route, due to the broad substrate specificity of RAMA.

The biologically active monosaccharide 3-deoxy-D-ura6//io-heptulosonic acid 7-phosphate (8 DAMP) is an important intermediate in the biosynthesis of aromatic amino acids in plants (the shikimate pathway). As shown in Scheme 2, this compound has been produced in a combined chemical and enzymatic synthesis from racemic V-acetylaspartate 3-semialdehyde (4) and DHAP (1). The four-step synthesis proceeds in an overall yield of 13% (37% for the aldolase reaction). The enzymatic step generates the required, enantiomerically pure, syn aldol adduct compound (5). In view of the broad range of substrates tolerated by FDP aldolase, this method may be applicable to the production of analogs of DAMP. 

The Claiscn rearrangement of chorismate 1, the last common intermediate in the biosynthesis of aromatic amino acids via the shikimate pathway, to prephenate 2 proceeds readily without catalysis263 and is greatly accelerated by a factor of 1.9 xlO6 by the enzyme chorismate mutase655-656. 

The mode of action of glyphosate is not yet fully understood. Jaworski (1972) found in investigations on Lemna gibba and Rhizobitun Japonicum bacteria that glyphosate inhibits the biosynthesis of aromatic amino acids. 

ABSTRACT This article describes recent developments in the chemistry of an important family of complex monosaccharides which have diverse structures and participate in a wide range of biological processes. For example 3-deoxy-D-/n nno-2-octulosonic acid (KDO) is a key component of the lipopolysaccharides (LPS) of Grammnegative bacteria, 3-deoxy-D-araftmo-2-heptulosonic acid (DAH) is a key intermediate in the biosynthesis of aromatic amino acids in bacteria and plants. A number of their syntheses that were achieved by homologation reactions of the natural carbohydrate units using enzymatic or chemical methods, as well as by total synthetic approaches are here included. Special emphasis is placed on new methodologies and their correlation with the biosynthetic pathway of the corresponding ulosonic acids. 

The ulosonic acids participate in many important biological processes. 3-Deoxy-D-ara6/ o-2-heptulosonic acid 7-phosphate (5) is a key intermediate in the biosynthesis of aromatic amino acids in plants and bacteria via shikimic acid pathway [6] and KDO (7) [1,5], DHA (6) [7-10] and KO (8) [4] are key components of the outer membrane of the lipopolysaccharides (LPS) of Gramm-negative bacteria, playing a crucial role in immunospecificity. Similarly act iV-acyl and O-acetyl derivatives of the various isomeric pseudoaminic acids of type 12, isolated from LPS... 

Figure 18 Allosteric regulation in the shikimate pathway for biosynthesis of aromatic amino acids in coli. Molecules that cause feedback inhibition are shown in red.

Figure 2L12 provides an overview of the biosynthesis of aromatic amino acids and histidine. Note that the aromatic amino acids are involved in pathways for the synthesis of lignin (a major constituent of woody tissue) and auxins (a class of plant hormones). 

Figure 21.12 Overview of the biosynthesis of aromatic amino acids and... 

---