Shikimic acid pathway

1. SHIKIMIC ACID PATHWAY
Presented by
Sonali S Gadge
Lecturer
P R Patil Institute of Pharmacy, Talegaon (SP), Dist-Wardha.

2. Phytoconstituents
(Phyto=Plant and Constituents= Chemicals)
 Living plants are solar powered biochemical and biosynthetic factory which
manufactures both Primary and Secondary metabolites.
Primary Metabolite Secondary Metabolite
Widely distributed in nature practically in all
organism.
Biosynthetically derived from primary
metabolite. It is more limited in distribution
restricted in taxonomic group.
Directly involved in growth, development
and reproduction (like carbohydrates,
proteins and fats)
Not directly involved in growth and
development. Involved in chemical adaption
to environmental stress, serves as protective,
defensive or offensive chemicals against
microorganisms, insects and higher
herbivorous animals.
Generally non-expensive to produce (to
isolate from plant/plant parts) ex-starch from
potato.
Generally expensive to produce. Ex- Quinine
from cinchona bark.
Present in plants in large quantity. Present in plants in much smaller quantity
than primary metabolites.

3. Simple in nature. Complex in nature.
Generally do not have only biological or
pharmacological action (Therapeutic value).
Have marked pharmacological action
(therapeutic activity) on human body.
Responsible for medicinal value of plants.
Ex- Carbohydrates (Starch, Cellulose,
Sugar)
Lipids (Fatty acids)
Proteins (Amino acids)
Alkaloids, Glycosides, Flavonoids, Resin,
Terpenoids.
Ex- Quinine in Cinchona bark.

4. Introduction to basic metabolic pathway
• The reaction sequence occurring within the organism in an orderly and
regulated way known as metabolic pathway.
Primary metabolic pathway of Carbon: A B C D

6. Introduction to Shikimic acid Pathway
 It is metabolic pathway for biosynthesis of Aromatic amino acid (
Phenyl alanine, Tyrosine and Tryptophan).
 Shikimic acid pathway (Shikimate pathway), is a metabolic pathway
used by bacteria, fungi, algae, some protozoans and plants for the
biosynthesis of aromatic amino acids (Phenylalanine, tyrosine and
tryptophan).
 Shikimic acid is the key intermediate from carbohydrates for
biosynthesis of C6-C3 unit (Phenyl propane derivative).
 This pathway is not found in animals (including humans), who must
instead obtain these essential amino acids from their diet.
 This can be through either the direct consumption of plants or
microorganisms or their indirect consumption via the consumption of
other animals.

7. Enzymes involved in the Shikimate Pathway
1. DAHP Synthatase
2. 3-dehydroquinate dehydratase
3. Shikimate dehydrogenase
4. Shikimate kinase
5. EPSP Synthatase
6. Chorismate synthatase
Biosynthetic Precursor
1. Phosphoenol pyruvate
2. Erythrose -4-phosphate
3. Nitrogen from other amino acids-Glutamate, Glycine, Serine

8. Shikimic acid
 Commonly known as its anionic form shikimate, is a
cyclohexene, a cyclitol and a cyclohexanecarboxylic acid.
 It is an important biochemical metabolite in plants and
microorganisms.
 Its name comes from the Japanese flower Shikimi, the
Japanese star anise, Illicium anisatum from which it was
isolated in 1885 by John Fredrick Eykman.
 The elucidation of its structure was made nearly 50 years later.
 Shikimic acid is also the glycoside part of some hydrolysable
tannins.

11. • Phosphoenol pyruvate (From Glycolysis) and Erythrose-4-Phosphate
(From Pentose phosphate pathway) react to form 2-keto3-
deoxy7posphoglucoheptonic acid, in a reaction catalyzed by the enzyme
DAHP Synthase.
• 2-keto3-deoxy7phosphoglucoheptonic acid is then transferred to 3-
dehydroquinate(DHQ), in a reaction catalyzed by DHQ Synthase.
• DHQ is dehydrated to 3-dehydroshikimic acid by the enzyme 3-
dehydroquinate dehydratase, which uses nicotinamide adenine
dinucleotide phosphate (NADPH) as a cofactor.
• The next enzyme Shikimate Kinase, an enzyme that catalyzes the ATP-
dependent phosphorylation of shikimate to form shikimate 3-shikimate 3-
phosphate. Shikimate phosphate is then coupled with phosphoenol
pyruvate to give 5-enolpyruvylshikimate-3-phosphate via the enzyme 5-
enolpyruvylshkimate-3-phosphate (EPSP) synthase.
• Then 5-enolpyruvylshikimate-3-phosphate is transformed into chorismate
by a Chorismate synthase.
• Prephenic acid then synthesized by a Claisen rearrangment of chorismate
by Chorismate mutase.
• Prephenate is oxidatively decarboxylated with retention of the hydroxyl
group by Prephenate dehydrogenase to give p-hydroxyphenylpyruvate,
which is transaminated using glutamate as the nitrogen source to give
tyrosine.

12. Role of Shikimic acid Pathway
1. Starting point in the biosynthesis of Phenolics
Phenyl alanine and tyrosine are the precursors used in the biosynthesis of
Phenylpropanoids. The Phenylpropanoids are then used to produce the
flavonoids coumarins, tannins and lignin.
2. Gallic acid biosynthesis
Gallic acid is formed from 3-dehydro-shikimate by the action of enzyme
shikimate dehydrogenase to produce3,5-didehyroshikimate. The later
compound spontaneously rearranges to gallic acid.
3. Other compounds
• Shikimic acid is a precursor for:
Indole, Indole derivatives and aromatic amino acids tryptophan and
Tryptophan derivatives such as the psychedelic compound
dimethyltryptamine.
Many alkaloids and other aromatic metabolites.

13. Uses
 In the pharmaceutical industry, shikimic acid from the Chinese star anise
(Illicium verum) is used as a base material for production of Oseltamivir
(Tamiflu).
• 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 synthesize (6S)-6-fluroshikimic acid, an antibiotic
which inhibits the aromatic biosynthetic pathway.
• Glyphosate, the active ingredient in the herbicide Roundup, kills plants by
interfering with the shikimate pathway in plants. More specifically,
glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate
synthatase (EPSPS).