3. Specialized Metabolism

Terpenoids: derived from IPP

-          Menthol

-          Stigmasterol

Alkaloids: contain one or several N, derived from amino acids

-          Morphine

-          Reserpine

Phenylpropanoids: derived from shikimate or malonate/acetate pathway

-          Coumarins like warfarin

-          Flavones like quercetin

Mevalonate/ pathway (cytosol/ER): ABA, strigolactons

DOXP pathway (plastids): Sterols, brassinosterol, sesquiterpenes, gibberellins

Both starts with pyruvate

Plastids: directly used, DOXP as an intermediate

Cytosol: cleaved into acetyl-CoA first

General prerequisite: IPP has two mesomeric forms both of which are necessary for the reaction.

Head-to-tail addition: cleavage of pyrophosphate, formation of a stabilized allyl cation, nucleophilic addition of the donor IPP (important: remember that PP is cleaved from the substance with the double bond located in alpha position to the PP)

Head-to-head addition:

Synthesis of IPP

-          Either via the mevalonate pathway or the DOXP pathway

Prenyl diphosphate homolog formation (terpene formation)

-          Via repetitive addition of IPP to form IPP oligomers

-          Prenyl transferases à methyl branches, no conjugated double bonds

-          Formation can take place either head-to-tail, head-to-head or head-to-middle

Terpenoid skeleton formation

• Specific terpene synthases are involved.

  • Similar reaction to prenyl transferases but intramolecularly, leading to cyclizations

• Depending on where the charge of the allylic cation is localized, different products are produced

  • Enzymes have a small percentage of side products

  • Alteration of the active center can result in the formation of different product composition

• Example: limonene synthase

Secondary modifications

• Redox reactions, isomerization reactions, conjugation reactions

• Often catalyzed by NADP+-dependent cytochrome P450 oxidases

• Alkaloids are heterocyclic (mostly), nitrogen-containing and basic

• Generally, they are very diverse and cannot be classified easily

• They are devided into three groups:

  • True Alcaloids, e.g. nicotin

    • Contain nitrogen in a heterocycle

    • Are derived from amino acids

  • Protoalkaloids, e.g. meskalin

    • Contain nitrogen but not in the heterocycle

    • Are derived from amino acids

  • Pseudoalkaloids (not derived from amino acids but, e.g., from acetate), e.g. coniin

• Catechins: Epigallocatechin gallate

• Flavones: Quercetin

• Isoflavones: Genistein

• Stilbenes: Resveratrol

• Coumarins: Warfarin

• Lignans: Podophyllotoxin

• Polyketides: Tetrahydrocannabinol

Lignans (H/S/G lignin), lagnans (pinoresinol),  and “volatiles” (?) (benzaldehyde).

Phenylpropanoid biosynthesis always starts from phenylalanine. Phenylalanine ammonia lyase (PAL) converts it to trans-cinnamic acid which is then converted to coumaric acid via P450 monooxygenase (cinnamic acid 4-hydroxylase). Other monooxygenases and methyl transferases produce ferulic acid and sinapic acid. Those four molecules build the core structures of phenylpropanoid biosynthesis.

• Lignins: oligomers

• Lignans: dimers

Gibberellins (GA)

• DOXP pathway —> IPP

• Prenyl transferase elongation reactions until geranylgeranyl diphosphate —> ent-kaurine

• All steps until ent-kaurene take place in the plastid

• Transport of ent-kaurine to the ER, oxidative modifications —> gibberellines

• (fungi have a different pathway to be able to manipulate the plant pathway without impairing their own)

Abscisic acid (ABA)

• DOXP pathway, prenyl transferase elongation until C40 (tetraterpene)

• Modifications to form zeaxanthin, then:

Strigolactones

• DOXP pathway, prenyl transferase elongation until C30, carotene precursor is formed

Also: brassinosterols derived from squalene, cyclization, oxidation of the b-ring, modification

Gibberellines: start as well with ent-kaurine but with different enzymes, different steps for oxidative modifications

Abscisic acid: fungal pathway is completely independent of the plant pathway (and much shorter, starting with C15)

Auxin: agrobacterium has a different pathway than plants

(Also: coronatin (specialized metabolite synthesized by bacteria))

Gibberellins

Activation via β3-hydroxylation:

Inactivation by β2-hydroxylation:

Salicylic acid

Inactivation by hydroxylation and conjugation

Oxidative modification

Conjugation

With examples!

NHP (?)

• C40 – in plants: precursor zeaxanthin (C40) in the plastid, broken down until xanthoxin is produced, export to cytoplasm, oxidations

• C15 – in fungi: precursor farnesyl diphosphate (C15), much shorter, independent from plant pathway