Shikimate biosynthetic pathway

The shikimate biosynthetic pathway occurs in bacteria, plants, and fungi (including yeasts) and is a major entry into the biosynthesis of primary and secondary metabolites, for example aromatic amino acids, menaquinones, vitamins, and antibiotics [1], Starting from erythrose-4-phosphate (E4P) and phosphoenol-pyruvate... 

Scheme 6.4.1. The shikimate biosynthetic pathway. The enzymes involved are (1) 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, (2) dehydroquinate synthase, (3) 5-...

Scheme 4.12 Catalytic antibody 1F7 was raised against the transition state analog 28 and possesses modest chorismate mutase activity. It can complement a permissive yeast strain that is auxotrophic for phenylalanine and tyrosine by replacingthe natural enzyme (CM) in the shikimate biosynthetic pathway.

Chorismic acid 360 is known to be a key intermediate in the shikimate biosynthetic pathway that bacteria and lower plants use to convert carbohydrates into aromatic compounds. 

McDonald, M. and Mavrodi, D. V. 2001. Phenazine biosynthesis in Pseudomonas fluorescens Branchpoint from the primary shikimate biosynthetic pathway and role of phenazine-... 

C7H13O10P 288.147 Enzymatically cyclised to 3-dehydroqui-nate in the aromatic shikimate biosynthetic pathway. [ ]d +18 (c, 0.5 in H2O) (as Ca salt). 

The rearrangement of 122 to 123 is a key reaction along the shikimate biosynthetic pathway for generating aromatic amino acids in plant, fungal, and bacterial systems, and it is catalyzed by the enzyme chorismate mutase more than a millionfold. This has stimulated an in-depth investigation of the mechanism of the Claisen rearrangement. ... 

The handed book is constmcted in the logic of presenting the parallel development of biosynthesis and organic methodology and how these can be apphed in efficient syntheses of natural products. The book is divided into four sections each representing the four major biosynthetic pathways of natural products, namely, acetate, mevalonate, shikimate biosynthetic pathways, and the mixed biosynthetic pathways... 

Vitamins are classified by their solubiUty characteristics iato fat-soluble and water-soluble groups. The fat-soluble vitamins A, E, and K result from the isoprenoid biosynthetic pathway. Vitamin A is derived by enzymic cleavage of the symmetrical C q beta-carotene, also known as pro-vitamin A. Vitamins E and K result from condensations of phytyldiphosphate (C2q) with aromatic components derived from shikimic acid. Vitamin D results from photochemical ring opening of 7-dehydrocholesterol, itself derived from squalene (C q). 

Quinones represent a very large and heterogeneous class of biomolecules. Three major biosynthetic pathways contribute to the formations of various quinones. The aromatic skeletons of quinones can be synthesized by the polyketide pathway and by the shikimate pathway. The isoprenoid pathways are involved in the biosynthesis of the prenyl chain and in the formation of some benzoquinones and naphthoquinones. ... 

Figure 1. Biosynthetic pathway for production of shikimic acid pathway-derived phenolic compounds in higher plants.

Deoxy-araWno-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36 The synthesis takes place at room temperature and neutral pH... 

Nature utilizes the shikimate pathway for the biosynthesis of amino acids with aryl side chains. These nonprotein amino acids are often synthesized through intermediates found in the shikimate pathway. In many cases, L-a-amino acids are functionalized at different sites to yield nonprotein amino acids. These modifications include oxidation, hydroxylation, halogenation, methylation, and thiolation. In addition to these modifications, nature also utilizes modified biosynthetic pathways to produce compounds that are structurally more complex. When analyzing the structures of these nonprotein amino acids, one can generally identify the structural similarities to one of the L-a-amino acids with aromatic side chains. 

Specific Control of Phytoalexin Accumulation by "Metabolite Shunting" of Biosynthetic Pathways. Graham and coworkers (personal communication), at the Monsanto Laboratories, St. Louis, have developed techniques to selectively shunt defensive metabolites, particularly of the shikimic acid cycle. Through various techniques, certain compounds are applied to plant aerial or root parts, and these compounds have the property of inducing specific accumulations of secondary metabolites. The directions of these accumulations are under known enzymic control (48), and the regulation of these enzymes is achieved by selecting appropriate inducers. Such inducers seem to provide a novel approach to the control of insects by magnifying the ability of plants to produce and concentrate antiherbivory compounds. 

In higher plants, anthraquinones are biosynthesized either via acylpolyma-lonate (as in the plants of the families Polygonaceae and Rhamnaceae) or via shikimic acid pathways (as in the plants of the families Rubiaceae and Gesneriaceae) as presented in the following biosynthetic schemes. 

All carbons are derived from either erythrose 4-phosphate (light purple) or phosphoenolpyruvate (pink). Note that the NAD+ required as a cofactor in step (3) is released unchanged it may be transiently reduced to NADH during the reaction, with formation of an oxidized reaction intermediate. Step (6) is competitively inhibited by glyphosate (COO—CH2—NH—CH2—PO ), the active ingredient in the widely used herbicide Roundup. The herbicide is relatively nontoxic to mammals, which lack this biosynthetic pathway. The chemical names quinate, shikimate, and chorismate are derived from the names of plants in which these intermediates have been found to accumulate. 

The mutants that grew in the presence of shikimic acid evidently had the biosynthetic pathway blocked... 

Isoprenoid structures for carotenoids, phytol, and other terpenes start biosynthetically from acetyl coenzyme A (89) with successive additions giving mevalonate, isopentyl pyrophosphate, geranyl pyrophosphate, farnesyl pyrophosphate (from which squalene and steroids arise), with further build-up to geranyl geranyl pyrophosphate, ultimately to a- and /3-carotenes, lutein, and violaxanthin and related compounds. Aromatic hydrocarbon nuclei are biosynthesized in many instances by the shikimic acid pathway (90). More complex polycyclic aromatic compounds are synthesized by other pathways in which naphthalene dimerization is an important step (91). 

The biosynthesis of flavonoids, stilbenes, hydroxycinnamates, and phenolic acids involves a complex network of routes based principally on the shikimate, phenyl-propanoid, and flavonoid pathways (Figs. 1.35 and 1.36). These biosynthetic pathways constitute a complex biological regulatory network that has evolved in vascular plants during their successful transition on land and that ultimately is essential for their growth, development, and survival [Costa et al., 2003]. 

Figure 1.37 Proposed biosynthetic pathway of curcuminoids in tumeric. Enzyme abbreviations CCOMT, caffeoyl-CoA O-methyltransferase 4CL, 4-coumarate CoA ligase CST, shikimate transferase CS3 H, p-coumaroyl 5-O-shikimate 3 -hydroxylase OMT, O-methyltransferase PKS, polyketide synthase. [Adapted from Ramirez-Ahumada et al. (2006)]...

Phenylpropanoids have an aromatic ring with a three-carbon substituent. Caffeic acid (308) and eugenol (309) are known examples of this class of compounds. Phenylpropanoids are formed via the shikimic acid biosynthetic pathway via phenylalanine or tyrosine with cinnamic acid as an important intermediate. Phenylpropanoids are a diverse group of secondary plant compounds and include the flavonoids (plant-derived dyes), lignin, coumarins, and many small phenolic molecules. They are known to act as feeding deterrents, contributing bitter or astringent properties to plants such as lemons and tea. 

Figure 4. Shikimate-derived metabolism in plants. A complicated biosynthetic pathway is a possible genetic engineering target.

Scheme 10. Possible biosynthetic routes leading from the shikimic acid pathway to betalains and the coexisting flavonoids (excluding anthocyanins) in betalain-bearing members of the Caryophyl-lales.

Fo, 35), which is an analog of riboflavin, serves as the business end of coenzyme F420 (36, Fig. 3), whose designation is based on its characteristic absorption maximum at 420 mn. Factor Fo is biosynthesized from the pyrimidine type intermediate 23 of the riboflavin biosynthetic pathway, which affords the pyrimidine ring and the ribityl side chain, whereas the car-bocyclic moiety is derived from the shikimate pathway via 4-hydroxyphenylpyruvate (56, 57). In contrast to the coenzymes described below, deazaflavin-type coenzymes are not strictly limited to methanogenic bacteria and are also found in strepto-mycetes and mycobacteria. 

The tetrapyrrole-type coenzyme F430 (19) was named on basis of its absorption maximum at 430 mn. The nickel-chelating factor is biosynthesized via the porphyrin biosynthetic pathway (Fig. 2) (19). For the handling of one-carbon fragments that play a central role in their metabolism, methanogenic bacteria use methanopterin (34, Fig. 3). The tetrahydropterine system that serves as the business end of the methanopterin coenzyme family is structurally similar to tetrahydrofolate, and the biosynthetic pathway starting from GTP is similar to that of tetrahydrofolate (Fig. 3). The ribitylaniline moiety is derived from ribose and from the shikimate pathway via 4-amino-benzoate (55). 

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