Shikimic acid

Shikimic acid
IUPAC name	(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid
Identifiers
CAS number	[138-59-0]
EC number	205-334-2
SMILES	O[C@@H]1CC(=C[C@@H](O)[C@H]1O)C(=O)O
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
Properties
Molecular formula	C7H10O5
Molar mass	174.15 g mol−1
Melting point	185–187 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references

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.^[1][2][3]

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).

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

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.

Biosynthesis of shikimic acid from 3-dehydroquinate

References

External links

• Shikimate and chorismate biosynthesis