Shikimic path

Enolpyruvylshikimate-3-phosphate (EPSP) synthase is where the money lies. Its identification by Nikolas Amrhein and Hans Steinriicken as the site of action of the blockbuster herbicide glyphosate awakened commercial interest in the shikimate path-... 

Ring from phenylalanine (shikimic acid path ... 

Figure 3. Hypothetical alternative enzyme path between 3-dehydroquinate and shikimate. A reversed order of the dehydratase and dehydrogenase steps of the classical pathway (top) would produce the quinate route (bottom).

This review will compare the strategies taken by synthetic chemists to produce natural products with the strategies utilized by nature. What types of molecular scaffolds are made in each case in the process of assembling a natural product Rarely will the paths be identical, but are there features that reveal a more universal logic in the construction of these molecules Or, by contrast, are there fundamental distinctions between organic synthesis and biosynthesis To answer these questions we have chosen - from a biosynthetic point of view - a diverse selection of secondary metabolites, ranging from relatively simple terpenes and shikimate-derived... 

Scheme 3.6 Bioindigo-Shikimic acid path (simplified). Preparation of indigo by bacterial de novo synthesis.

When such strains as E. coli 83-24, which are blocked after shikimic acid, were grown on minimal medium plus aromatic supplement, they accumulated 400-800 mg. of shikimic acid per liter, together with variable amounts of shikimate 5-phosphate. Since no mutants that are blocked between shikimic acid and its phosphorylated form were found, it was considered that the phosphate ester is not on the main path of biosynthesis. As will be pointed out later, enzymic studies showed that shikimate 5-phosphate is actually an intermediate between shikimate and the aromatic compounds. It would appear, therefore, that the block in such strains as E. coli 83-24 is probably immediately after shikimate 5-phosphate. With filtrates from this organism, methods were developed for the isolation of pure shikimate and for its stepwise degradation. ... 

Miscellaneous Alkaloids. Shikimic acid (57) is a precursor of antliranilic acid (28) and, in yeasts and Escherichia coli (a bacterium), antliranilic acid (o-aminobenzoic acid) is known to serve as a precursor of tryptophan (26). A similar but yet unknown path is presumed to operate in higher plants. Nonetheless, antliranilic acid itself is recognized as a precursor to a number of alkaloids. Tims damascenine [483-64-7] (134), C10H13NO3, from the seed coats of Tdigella damascena has been shown (95) to incorporate labeled antliranilic acid when unripe seeds of the plant are incubated with labeled precursor. 

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. 

The biosynthetic pathway (Figure 10.5) of polyphenols, including phenolic acids is well known. Phenylalanine formed in plants via the shikimate pathway is a common precursor for most of the phenolic compounds. Forming hydroxycinnamic acids from phenylalanine requires hydroxylation and methylation steps. The formation of hydroxybenzoic acids is simple and they can directly be formed from the corresponding hydroxycinnamic acids with the loss of acetate or with an alternate path stemming from an intermediate in the phenylpropanoid pathway [69,77,78]. 

Experiments with (2S,3R)- and (2/, 35 )-[3- H]phenylalanines gave tritium retentions of 44% and 24%, respectively (Vederas and Tamm, 1976). Simultaneous incorporation of equal amounts of both enantiomers led to the expected 34% retention of hydrogen label. Transamination occurs stereo-specifically at position 2 of the amino acid therefore, the participation of at least two enzymes with different stereochemical requirements at the 3 position is reasonable. Two biosynthetic pathways are consistent with the data available (see Fig. 13). Path A in Fig. 13 depicts (2 S )-phenylalanine as the actual precursor which is in rapid equilibrium with its enantiomer in path B phenylpyruvic acid (49), derived directly from shikimic acid, is the primary precursor. Considerable suppression of the incorporation of D-amino acid by phenylpyruvic acid (49) indicated that the naturally abundant L-enantiomer is the actual primary precursor, thus demonstrating that path A (Fig. 13) is probably the main biosynthetic route. Both enantiomers are in rapid equilibrium with phenylpyruvic acid (49) via the action of aminotransferases or amino acid oxidases. The stereochemistry of hydrogen loss... 

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