Shikimic acid pathway

• Dr. R.N.Lahoti Institute of Pharmaceutical

Education and Research Center
1.DAHP Synthesis :Phosphoenolpyruvate + erythrose-4-phosphate
=2-keto-3-deoxy-7-phosphoglucoheptonic acid
1. Enzyme :DAHP synthase.
2.3-dehydroquinate (DHQ) from DAHP / cyclization reaction
1. 2nd carbon ketone group converted to hydroxyl group.
2. Phosphate group from 7th carbon get released as phosphoric acid .
3. 6th carbon oxidation to form ketone group.
4. Enzyme : 3-DHQ synthase.
5. Co factor :
1. NAD is required but regenerated, so no net NAD is consumed.
2. Cobalt
1.3-dehydroshikimic acid synthesis from 3-dehydroquinate
1. Dehydration reaction
2. 2nd carbon hydroxyl group release as water molecule and form a double bond.
3. Enzyme 3-dehydroquinate dehydratase
1.Formation of shikimic acid
1. Co Enzyme shikimate dehydrogenase using NADPH.
2. At 6th carbon ketone group converted to hydroxyl group
3. Hydrogen atom is obtained from NADPH to from NAD.
1.Formation of shikimic acid 3 phosphate
1. Enzyme Shikimate kinase adds a phosphate to shikimic acid .
2. phosphate group from ATP.
3. ATP is converted to ADP.
4. ATP dependent phosphorylation of shikimate .
1.Addition of Phophspoenol pyruvate to form 5 –Enol Pyruvyl Sikimic acid
Phosphate EPSP
1. 5th Water molecule get released
2. Phosphate group from phosphoenol pyruvate release as phosphoric acid
3. Enzyme is EPSP synthetase
1.Formation of Chorisimic acid
1. Phosphate group get released to form a double bond
2. Enzyme chorismic acid synthetase
3. Branching point
1. Antharnilic acid
2. Prephanic acid
1.Formation of prephenate
2.Enzyme Chorismate mutase
3.Claisen rearrangement.
1. formation of phenyl pyruvic acid
2. Enxyme Prephenate dehydrogenase
3. then oxidatively decarboxylates prephenate, keeping the hydroxyl
group,
1. -HCOO as CO2
2. OH as Water get released
4. Ring aromatization , benzene ring is formed
• This compound is transaminated with glutamate, producing
tyrosine and α-ketoglutarate
1. Reductive transamination
2. This compound is transaminated with glutamate, producing
phenylalanine
3. Glutamine to glutamate
4. Alpha ketoglutamic acid
5. Enzyme : phenylalanine transaminase.
1. Formation of para hydroxy phenyl pyruvic acid
2. then oxidatively decarboxylation of prephenate, keeping the
hydroxyl group,
1. Carboxylatio -HCOO as CO2
2. Dehydrogenation :NAD to NADH
3. Ring aromatization , benzene ring is formed
4. Enzyme :prephenate dehydrogenase
• This compound is transaminated with glutamate, producing
tyrosine and α-ketoglutarate
1. Reductive transamination
2. This compound is transaminated with glutamate, producing
Tyrosine
3. Glutamine to glutamate
4. Alpha ketoglutamic acid
Applications of shikimic acid
pathway
1. Biosynthesis of Aromatic Amino Acids
• Produces phenylalanine, tyrosine, and tryptophan, essential for protein
synthesis.
• These amino acids are precursors for neurotransmitters, hormones, and
other bioactive molecules.
2.Leads to the formation of:
• Flavonoids – antioxidants and UV protectants.
• Lignin – structural polymer in plant cell walls.
• Tannins – defense compounds with astringent properties.
• Coumarins and alkaloids – involved in plant defense and
pigmentation
3. Shikimic acid from Chinese star anise is used to make oseltamivir
(Tamiflu) in pharma.
4. Glyphosate, in Roundup herbicide, kills plants by blocking the shikimate
pathway enzyme EPSPS. "Roundup Ready" GM crops resist this.
Actate pathway
1. Synthesis of secondary metabolites
2. Starting material is acetate in the form active form as acetate co Enzyme A.
3. Acetate neutralize and as central molecule int his pathway.
4. Straight chain compound and aromatic compound.
5. Two main route in this pathway
1. Actate mevalonate pathway / isoprenoid (C2H5)pathway
1. Terpenes (Mono,sesqui, di, tri)and steroids in plants
2. Acetate melonate path
1. Starting material Acetyl Co enzyme A
2. Melonic acid is one of the intermediate produces
1. Fatty acid
2. long chain fatty acid
3. Poly ketoids
Importance of Isoprenoid path
Isoprene unit C5H8
(two double bond )
1. Different no Isoprene units combine in
different numbers to form Different
terpenes
2. Terpenoids: oxygenated derivative such
as
1. Hydroxy group
2. ketone,
3. aldehyde is get attached
Two isoprene unit combines to form a Monoterpenoids
(C10)
Eg. Menthol(C10 ), geraniol

Sesquiterpenoids = three isoprene unit (C5x3)= 15

carbon
Eg. termeron

Diterpenoids =C5x 4isoprene = 20 C

Eg .phytol
Acetyl Co A +Acetyl =aceto acetyl CoA +Acetyl Co A
Co A

= HMG CoA
(Beta Hydroxy Methyl Glutaryl CoA)
HMG CoA reductase (reduction)=
Mevolonate
IPP(C5) DMAPP(C5)

GERANYL PYROPHOSPHATE (C10) Monoterpenes

Menthol,limonen(citrus peel),
geroniol(Rose), linalool(spices
Coriander),Alpha piene,citral
IPP(C5)

Fernesyl pyrophosphate (C15) Sesquiterpenoids

Santalene(santlum album oil),
Turmerone,Zingiberene, abscicic acid
(PH)
Fernesyl
pyrophosphate
(C15)
Squalene (C30) After Cyclization forms
cyclopentano per hydro phenathrene
ring = form steroidal compound
1. Eg.
1.1. Sigma sterol (steroids)
1.2. Diosgenin(Discorea)
1.3. Solanine (Solanum species )
2. Tripenoid
2.1. Penta cyclic triterpenoids
2.1.1. Glycirhizinic acid
2.2. Tetra cyclic
IPP(C5) Fernesyl pyrophosphate (C15)

Geranyl geranyl pyrophosphate (C20) (4 . 5C) Diterpenoids

Eg.taxol
Precusor gibraline (PH), phytols
(chlorophyll)
Geranyl geranyl Tetraterpenes c5x 08 Eg. Carotenes, lycopenes , carotenoids
pyrophosphate
(C20) (4 . 5C)