OIA2007 SHIKIMIC ACID PATHWAY

Shikimic Acid Pathway

A biosynthetic pathway in plants & microbes that produces aromatic amino acids and phenolic compounds.

Organisms with Shikimate Pathway

Found in plants, fungi, bacteria, but not in animals (hence, target for antibiotics/herbicides).

Shikimic Pathway Origin

Starts from phosphoenolpyruvate (PEP) and erythrose-4-phosphate, both derived from glycolysis and the pentose phosphate pathway.

First Product (Shikimic)

Shikimic acid via cyclization and condensation of intermediates.

End Product (Shikimic)

Aromatic amino acids: Phenylalanine, Tyrosine, and Tryptophan.

PEP (Phosphoenolpyruvate)

3-carbon donor in the first condensation step.

Erythrose-4-phosphate (E4P)

4-carbon sugar that reacts with PEP.

3-Dehydroshikimate → Shikimic Acid

Formed through cyclization and reduction.

Shikimic Acid → Chorismic Acid

Involves ATP, pyruvate, PEP hydrolysis, and multiple rearrangements.

Chorismic Acid → Branch Point

Precursor for tryptophan, phenylalanine, tyrosine, and phenolic compounds.

Shikimate Dehydrogenase

Reduces 3-dehydroshikimate → shikimic acid using NADPH.

Chorismate Synthase

Converts shikimate → chorismate (in presence of ATP and PEP).

Anthranilate Synthase

Converts chorismate → anthranilic acid (tryptophan branch).

Prephenate Synthase

Converts chorismate → prephenic acid (phenylalanine & tyrosine branch).

Prephenate Dehydratase / Dehydrogenase

Convert prephenate → phenylpyruvate or hydroxyphenylpyruvate.

Phenylalanine

Made from prephenic acid via phenylpyruvate.

Tyrosine

Formed from 4-hydroxyphenylpyruvate.

Tryptophan

Synthesized via anthranilic acid + phosphoribosyl pyrophosphate (PRPP).

Phenylpropanoids (C6-C3)

Derived from phenylalanine. Includes cinnamic acid, lignin, coumarins.

Phenyl-C1 Compounds

Formed by cleavage of side chains (e.g., benzaldehyde).

Flavonoids

Includes quercetin, kaempferol; derived from phenylpropanoids.

Tannins

Polyphenolic compounds derived from shikimate-pathway products.

Coumarins

Formed from phenylpropanoid backbone.

Alkaloids

Some classes like tryptamine alkaloids come from tryptophan.

Eugenol

Found in clove oil, derived from phenylpropanoids.

Vanillin

Comes from ferulic acid, a phenolic derivative.

Reserpine

Found in Rauwolfia spp., derived from tryptophan.

Quinoline & Isoquinoline Alkaloids

Precursors: tyrosine & phenylalanine.

Shikimic Acid

Precursor for oseltamivir (Tamiflu) in pharmaceuticals.

Primary Metabolites

Found in all organisms (e.g., amino acids, sugars), essential for life.

Secondary Metabolites

Found in specific plant families, used for defense, attraction, survival.

Examples of Primary Metabolites

Starch, glucose, fatty acids.

Examples of Secondary Metabolites

Flavonoids, alkaloids, tannins, essential oils.

Antibiotic Targets

Humans lack this pathway → good target for antibiotics/herbicides (e.g., glyphosate).

Analgesic/Antipyretic Properties

Seen in phenolic derivatives like salicylic acid (from shikimate pathway).

Antioxidants

Flavonoids and phenolics from this pathway have free radical scavenging activity.

Anti-inflammatory & Anticancer

Many phenylpropanoids show anti-inflammatory and cytotoxic effects.

Shikimate Pathway Assay

Monitored via GC-MS or LC-MS to identify intermediate build-up.

Engineering Plants for Production

Metabolic engineering of this pathway used to enhance metabolite yield.

Example Drug Precursor

Shikimic acid as a key industrial precursor for antiviral drugs.