Chorismic acid biosynthesis

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... 

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

Aromatic amino acid biosynthesis proceeds via a long series of reactions, most of them concerned with the formation of the aromatic ring before branching into the specific routes to phenylalanine, tyrosine, and tryptophan. Chorismate, the common intermediate of the three aromatic amino acids, (see fig. 21.1) is derived in eight steps from erythrose-4-phosphate and phosphoenolpyruvate. We focus on the biosynthesis of tryptophan, which has been intensively studied by both geneticists and biochemists. 

Chloramphenicol.—A synthetase which converts chorismic acid into p-amino-phenylalanine (an intermediate in chloramphenicol biosynthesis) has been partly characterized it requires an aminotransferase and pyridoxal phosphate for activity.58... 

Fig. 6 Four enzymes (one salicylate-AMP ligase YbtE/PchD, two NRPS and/or NRPS/PKS enzymes HMWPl/PchE and HMWP2/PchF, and one reductase YbtU/PchG) are required for the in vitro biosynthesis of (a) yersiniabactin (24) and (b) pyochelin (25). (c) The initial stages of 24 and 25 biosynthesis proceed via a similar mechanism from chorismic acid 26 to the salicylate-bisthiazole intermediate 33...

Fig. 12 The initial stages of 64, 65, and 66 biosynthesis proceed via the same mechanism, with the condensation of DHB (75) (from chorismic acid 26) with a PCP-tethered amino acid 80 (serine (a), lysine (b), or threonine (c), respectively)...

Campbell, M.M. et al. The Biosynthesis and Synthesis of Shikimic Acid, Chorismic Acid, and Related Compounds. 1993 [45]... 

Fig. 8.15 Biosynthesis of L-Phe. Compounds EPSP, 5-enol-pyruvoylshikimic acid-3-phosphate CHA, chorismic acid PPA, prephenic acid PPY, phenylpyruvic acid S3P, shikimic acid 3-phosphate.

The 4-aminobenzoate moiety of tetrahydrofolic acid is obtained from the shikimate pathway of aromatic amino acid biosynthesis via chorismate. Interestingly, apicomplexan protozoa may have conserved the complex shikimate pathway for the single purpose to generate 4-aminobenzoate as a tetrahy-drofolate precursor, whereas aromatic amino acids are obtained from external sources. 

Several studies of the biosynthesis of chloramphenicol have led to the conclusion that it is formed via the shikimic acid pathway, specifically from chorismic acid. An arylamine synthetase promotes formation of p-amino-L-phenyl alanine (1 ) 50>51. This product is converted to chloramphenicol (15) by oxidation of the amine function to a nitro group, by hy-droxylation of the benzylic methylene group, reduction of the carboxyl... 

In the treated plants the biosynthesis of phenylalanine, more particularly the metabolism of chorismic acid, is inhibited. Similar conclusions were drawn by Roisch and Lingens (1974) in experiments with Escheria coli. 

Amino acid biosynthesis is often regulated by the end products of a given pathway to control the relative amounts of amino acids being produced. Aromatic amino acid biosynthesis thus far is known to be feedback regulated at three points in the shikimate/chorismate pathway. The initial step is catalyzed by 3-deoxy-D-arabino-2-heptulosonate-7-... 

Isochorismate synthase, that might be involved in the biosynthesis of 2,3-DHBA, has recently been purified from Catharanthus roseus cell-suspension cultures and subsequently its gene was cloned (L. van Tegelen, P. Moreno, A. Croes, G. Wullems and R. Verpoorte, submitted for publication). Two isoforms of the enzyme were purified and characterized. Both have an apparent molecular mass of 65 kD. The Km values for chorismic acid are 558 pM and 319 p.M for isoform I and II respectively. The enzymes are not inhibited by aromatic amino acids and require Mg for enzyme activity. The isolated cDNA encodes a protein of 64 kD with a A-terminal chloroplast targeting signal. The deduced amino acid sequence shares homology with bacterial isochorismate synthases, and also with anthranilate synthases, another chorismate utilizing enzyme. 

Salicylic acid biosynthesis along the chorismate/isochorismate pathway... 

The first intermediate in the biosynthesis of 2,3-DHBA in K. pneumoniae is isochorismic acid. The conversion of chorismic acid to isochorismic acid requires Mg ... 

Enzymes and genes involved in the 2,3-DHBA biosynthesis When in 1968 the intermediates of 2,3-DHBA biosynthesis were identified [85], it became clear that isochorismate synthase (isochorismate hydroxy mutase) is the enzyme that converts chorismic acid to isochorismic acid. 2,3-Dihydro-2,3-DHBA synthase (or isochorismatase) converts isochorismic acid to 2,3-dihydro-2,3-DHBA and finally... 

A feedback inhibition has been detected in B. subtilis, using the ferrisiderophore reductase. This enzyme reduces iron from the ferrisiderophore. The rate at which the ferrisiderophore reductase reduces iron from ferrisiderophores may signal the aromatic pathway about the demand for chorismic acid for 2,3-DHBA synthesis [128,129]. The reductase may have a regulatory effect on chorismate synthase activity. Chorismate synthase may have oxidizable sulfhydryl groups that, when oxidized, may slow the synthesis of chorismic acid [128-130]. There seemed to be no repression or inhibitory effect of 2,3-DHBA or SA on its own biosynthesis [78,121]. Also the endproduct mycobactin (sole endproduct) does not inhibit SA biosynthesis [78]. 

Claisen rearrangement of chorismic acid 1 to prephenic acid 2 (Scheme 1), which is catalyzed by the enzyme chorismate mutase, can be considered as the key step in the biosynthesis of aromatic compounds, that is the so-called shikimic acid pathway. The chair-like transition state geometry 3 was proved by double isotope-labeling experiments [2]. However, in the laboratory this particular reaction can be accelerated not only by enzymes but also by catalytic antibodies [3]. For the generation of such antibodies haptenes such as 4 were used, that is, molecules whose structure is very similar to the transition state of the particular reaction and which are tightly bound by the antibody. 

The naturally occurring naphthoquinones such as lawsone and juglone are products of the shikimic acid pathway to aromatic amino-acids but the path which leads to these naphthoquinones branches from the main pathway before the formation of aromatic compounds, probably no later than chorismic acid.It will be most interesting to see whether the biosynthesis of shihunine also follows this route all the other bases of plant origin which arise from products of the shikimic acid pathway derive from aromatic precursors. 

Candicidin production by Streptomyces griseus was inhibited by inorganic phosphate, which suppressed the biosynthesis of p-aminobenzoate, the starter unit for the synthesis of this 38-membered heptaene macrolide antibiotic [95]. P-aminobenzoic acid synthase (PABA synthase) catalyses the conversion of chorismic acid to PABA, which is a precursor to candicidin. 

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