Shikimic acid

Chembox new
Name = Shikimic acid
ImageFile = Shikimic-acid-skeletal.png ImageName = Chemical structure of shikimic acid
ImageFile1 = Shikimic-acid-3D-balls.png ImageName1 = 3D model of shikimic acid
IUPACName = (3"R",4"S",5"R")-3,4,5-Trihydroxy-
1-cyclohexenecarboxylic acid
Section1 = Chembox Identifiers
CASNo = 138-59-0
EINECS = 205-334-2
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
Section2 = Chembox Properties
Formula = C₇H₁₀O₅
MolarMass = 174.15 g/mol
MeltingPt = 185–187 °C

Shikimic acid, more commonly known as its anionic form shikimate, is an important biochemical intermediate in plants and microorganisms. Its name comes from the Japanese flower "shikimi" (シキミ, "Illicium anisatum"), from which it was first isolated.

Shikimic acid is a precursor for:
*the aromatic amino acids phenylalanine and tyrosine,
*indole, indole derivatives and aromatic amino acid tryptophan,
*many alkaloids and other aromatic metabolites,
*tannins, flavonoids, and lignin.

In the pharmaceutical industry, shikimic acid from the Chinese star anise is used as a base material for production of Tamiflu (oseltamivir). Although shikimic acid is present in most autotrophic organisms, it is a biosynthetic intermediate and generally 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 fruit, which is abundant in North America, in yields of around 1.5%, so just 4 kg of sweetgum seeds are enough for fourteen packages of Tamiflu. By comparison star anise has been reported to yield 3 to 7% shikimic acid. Recently biosynthetic pathways in "E. coli" have been enhanced to allow the organism to accumulate enough material to be used commercially. [cite journal
last = Bradley
first = David | date = 2005-12
title = Star role for bacteria in controlling flu pandemic?
journal = Nature Reviews Drug Discovery
volume = 4
pages = 945–946
url = http://www.nature.com/nrd/journal/v4/n12/full/nrd1917.html
format = html
accessdate = 2007-03-07
doi = 10.1038/nrd1917 ]

Biosynthesis

Phosphoenolpyruvate and erythrose-4-phosphate react to form 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP), in a reaction catalysed by the enzyme DAHP synthase. DAHP is then transformed to 3-dehydroquinate(DHQ), in a reaction catalysed by DHQ synthase. Although this reaction requires NAD as a cofactor, the enzymic mechanism regenerates it, resulting in the net use of no NAD (note that diagram is incorrect).

DHQ is dehydrated to 3-dehydroshikimate by the enzyme dehydroquinase, which is reduced by to shikimic acid by the enzyme shikimate dehydrogenase, which uses NADPH as a cofactor.

References

External links

* [http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/misc/shikim.html Shikimate and chorismate biosynthesis]