Shikimic acid

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Shikimic acid
Chemical structure of shikimic acid
Chemical structure of shikimic acid
3D model of shikimic acid
3D model of shikimic acid
Names
Preferred IUPAC name
(3R,4S,5R)-3,4,5-Trihydroxycyclohex-1-ene-1-carboxylic acid
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.004.850 Edit this at Wikidata
EC Number
  • 205-334-2
KEGG
UNII
  • InChI=1S/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1 checkY
    Key: JXOHGGNKMLTUBP-HSUXUTPPSA-N checkY
  • InChI=1/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1/f/h11H
  • InChI=1/C7H10O5/c8-4-1-3(7(11)12)2-5(9)6(4)10/h1,4-6,8-10H,2H2,(H,11,12)/t4-,5-,6-/m1/s1
    Key: JXOHGGNKMLTUBP-HSUXUTPPBZ
  • C1[C@H]([C@@H]([C@@H](C=C1C(=O)O)O)O)O
Properties
C7H10O5
Molar mass 174.15 g/mol
Melting point 185 to 187 °C (365 to 369 °F; 458 to 460 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Shikimic acid, more commonly known as its

Johan Fredrik Eykman.[1] The elucidation of its structure was made nearly 50 years later.[2]

Biosynthesis

DHQ synthase. Although this reaction requires nicotinamide adenine dinucleotide
(NAD) as a cofactor, the enzymic mechanism regenerates it, resulting in the net use of no NAD.

Biosynthesis of 3-dehydroquinate from phosphoenolpyruvate and erythrose-4-phosphate

DHQ is dehydrated to

3-dehydroshikimic acid by the enzyme 3-dehydroquinate dehydratase, which is reduced to shikimic acid by the enzyme shikimate dehydrogenase, which uses nicotinamide adenine dinucleotide phosphate
(NADPH) as a cofactor.

Biosynthesis of shikimic acid from 3-dehydroquinate

Shikimate pathway

Main article: Shikimate pathway

Biosynthesis of the aromatic amino acids

The shikimate pathway is a seven-step metabolic route used by

algae, parasites, and plants for the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan). This pathway is not found in animals; therefore, phenylalanine and tryptophan represent essential amino acids that must be obtained from the animal's diet (animals can synthesise tyrosine from phenylalanine, and therefore is not an essential amino acid except for individuals unable to hydroxylate phenylalanine to tyrosine
).

The seven enzymes involved in the shikimate pathway are

5-enolpyruvylshikimate-3-phosphate via the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase
.

Then 5-enolpyruvylshikimate-3-phosphate is transformed into

chorismate by a chorismate synthase
.

chorismate by chorismate mutase.[4][5]

Prephenate is

α-ketoglutarate
.

Starting point in the biosynthesis of some phenolics

phenylpropanoids biosynthesis. The phenylpropanoids are then used to produce the flavonoids, coumarins, tannins and lignin. The first enzyme involved is phenylalanine ammonia-lyase (PAL) that converts L-phenylalanine to trans-cinnamic acid and ammonia
.

Gallic acid biosynthesis

3,5-didehydroshikimate. This latter compound spontaneously rearranges to gallic acid.[6]

Other compounds

Shikimic acid is a precursor for:

Mycosporine-like amino acids

Mycosporine-like amino acids are small secondary metabolites produced by organisms that live in environments with high volumes of sunlight, usually marine environments.

Uses

In the pharmaceutical industry, shikimic acid from the Chinese

autotrophic organisms, it is a biosynthetic intermediate and in general found in very low concentrations. The low isolation yield of shikimic acid from the Chinese star anise is blamed for the 2005 shortage of oseltamivir. Shikimic acid can also be extracted from the seeds of the sweetgum (Liquidambar styraciflua) fruit,[2] which is abundant in North America, in yields of around 1.5%. For example, 4 kg (8.8 lb) of sweetgum seeds is needed for fourteen packages of Tamiflu. By comparison, star anise has been reported to yield 3% to 7% shikimic acid. Biosynthetic pathways in E. coli have recently been enhanced to allow the organism to accumulate enough material to be used commercially.[7][8][9] A 2010 study released by the University of Maine showed that shikimic acid can also be readily harvested from the needles of several species of pine tree.[10]

chiral building block can overcome these additional costs, for example, shikimic acid for oseltamivir
.

Aminoshikimic acid is also an alternative to shikimic acid as a starting material for the synthesis of oseltamivir.

Target for drugs

Shikimate can be used to synthesise

5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). "Roundup Ready" genetically modified crops overcome that inhibition.[13]

Occurrence

It occurs in tree fern fronds, a specialty called fiddlehead (furled fronds of a young tree fern in the order Cyatheales, harvested for use as a vegetable). These fronds are edible, but can be roasted to remove shikimic acid.[14]

Shikimic acid is also the glycoside part of some hydrolysable tannins. The acid is highly soluble in water and insoluble in nonpolar solvents, and this is why shikimic acid is active only against Gram-positive bacteria, due to outer cell membrane impermeability of Gram-negatives.[15]

See also

References

  1. ^ Eykman, J. F. (1881). "The botanical relations of Illicium religiosum Sieb., Illicium anisatum Lour". American Journal of Pharmacy. 53 (8).
  2. ^
    doi:10.1016/j.tetlet.2008.02.140
    .
  3. PMID 15012217
    .
  4. PMID 100134
    .
  5. doi:10.1021/jp972501l
    .
  6. ^ "Gallic acid pathway". metacyc.org.
  7. S2CID 30035056
    .
  8. ^ Krämer, M.; Bongaerts, J.; Bovenberg, R.; Kremer, S.; Müller, U.; Orf, S.; Wubbolts, M.; Raeven, L. (2003). "Metabolic engineering for microbial production of shikimic acid". Metabolic Engineering. 5 (4): 277–283.
    PMID 14642355
    .
  9. ^ Johansson, L.; Lindskog, A.; Silfversparre, G.; Cimander, C.; Nielsen, K. F.; Liden, G. (2005). "Shikimic acid production by a modified strain of E. coli (W3110.shik1) under phosphate-limited and carbon-limited conditions". Biotechnology and Bioengineering. 92 (5): 541–552.
    S2CID 19659961
    .
  10. ^ "Maine pine needles yield valuable Tamiflu material". Boston.com. 7 November 2010.
  11. ^ Song, Chuanjun; Jiang, Shende; Singh, Gurdial (4 August 2011). "Facile Syntheses of (6S)-6-Fluoroshikimic Acid and (6R)-6-Hydroxyshikimic Acid". Chemical Research in Chinese Universities. 18 (2): 146–152.
  12. PMID 8192477
    .
  13. PMID 16916934
    .
  14. S2CID 4175635
    .
  15. doi:10.3746/jfn.2009.14.3.195
    .

Books
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