Organic and biosynthesis
Crotti
20-10-2020
Natural products > fungi/bacteria > medicine
Organic compounds > primary metabolites (essential for life), e.g. carbohydrates, nucleic acids, fats,
AA > secondary metabolites: natural products (species specific, not essential for life, can be made out
of organic compounds).
Salicylic acid: plant hormone involved in infection response
Natural products as medicines:
- Possess broad chemical structure diversity
- Not produced by plant but with their ecological competitors
- Similar domains
Natural product biological activity: biological role of natural products
- End product of biosynthesis route (rubber)
- Attracting or repelling tools (essential oils, fragrances)
- Chemical weapon to gain advantages against other species (phytotoxins, phytoalexins,
antibiotics)
Chemical weapon – plant vs plant
- Allelopathy: one organism produces biochemicals (allelochemicals) that influence the growth
survival, development and reproduction of other organisms
- Phytotoxins: inhibition of other plants by poison or toxins, e.g. Juglone
Chemical weapon – plant vs microbes
- Phytoalexins: defence against attack, e.g. Viniferin and Resveratrol
Chemical weapons:
- Repellents: insecticides, e.g. Nicotine and Caffeine
- Antibiotics: chemical substances produced by microorganisms and having antagonistic effects
on the growth of other microorganisms
Applications of natural products:
- Drugs
- Toxins
- Fragrances, colours and flavours
- Others, e.g. Resins, Phenols, rubber, chemotaxonomy
More than 40% of new drug between 1981-2014 are from biological origin.
Digitoxin glycorandomization > digitoxigenin > anticancer potency and reduced inotropic activity.
, Secondary metabolism: the building blocks and construction mechanisms
The building blocks: very limited number
- C1: Carbon
- C2: Carbon
- C3: Fats, fatty acids, polyketides
- C4: Aromatic amino acids, phenylpropanoids
- C5: Terpenoids, steroids
- C6: Alkaloids
The building blocks: source and destination
- Shikimate route: aromatic amino acids, alkaloids
- Acetate route: simple carbon, fats/fatty acids/polyketides/flavonoids/steroids
- MVA/MEP route: isoprene units
- Acetate route-Krebs cycle: peptides/alkaloids
Assembly mechanisms:
- Alkylation: C-C (nucleophilic/electrophilic substitution/addition)
- Wagner-Meerwein rearrangements
- Aldol reaction / Claisen reaction: C-C
- Iminie formation / Mannich reaction: C-N
- Amino acids and transamination
- Decarboxylation
- Oxidation / reduction: C-C > C=C or C-OH > C=O
- Phenolic oxidative coupling C-C
- Halogenation reaction
- Glycosylation
Cofactors: compounds required for an enzyme’s activity to increase rate of a chemical reaction
- Prosthetic group: strong (covalently) bonded organic molecule, no protein
- Coenzyme (co-substrate): small organic substances, not covalent
e.g. NAD+, NADH, FAD, FADH2, ATP, ADP, CoA
Biosynthetic research: studying the sequence of reactions (=metabolic flux) and characterize the
enzymes in vivo. Nowadays, the intermediate molecules and enzymes can be studied.
Isotopic studies: isotopically labelled compound (precursor) > organism > produced metabolite >
isolation, purification, degradation, analysed > detect presence of isotope.
Crotti
20-10-2020
Natural products > fungi/bacteria > medicine
Organic compounds > primary metabolites (essential for life), e.g. carbohydrates, nucleic acids, fats,
AA > secondary metabolites: natural products (species specific, not essential for life, can be made out
of organic compounds).
Salicylic acid: plant hormone involved in infection response
Natural products as medicines:
- Possess broad chemical structure diversity
- Not produced by plant but with their ecological competitors
- Similar domains
Natural product biological activity: biological role of natural products
- End product of biosynthesis route (rubber)
- Attracting or repelling tools (essential oils, fragrances)
- Chemical weapon to gain advantages against other species (phytotoxins, phytoalexins,
antibiotics)
Chemical weapon – plant vs plant
- Allelopathy: one organism produces biochemicals (allelochemicals) that influence the growth
survival, development and reproduction of other organisms
- Phytotoxins: inhibition of other plants by poison or toxins, e.g. Juglone
Chemical weapon – plant vs microbes
- Phytoalexins: defence against attack, e.g. Viniferin and Resveratrol
Chemical weapons:
- Repellents: insecticides, e.g. Nicotine and Caffeine
- Antibiotics: chemical substances produced by microorganisms and having antagonistic effects
on the growth of other microorganisms
Applications of natural products:
- Drugs
- Toxins
- Fragrances, colours and flavours
- Others, e.g. Resins, Phenols, rubber, chemotaxonomy
More than 40% of new drug between 1981-2014 are from biological origin.
Digitoxin glycorandomization > digitoxigenin > anticancer potency and reduced inotropic activity.
, Secondary metabolism: the building blocks and construction mechanisms
The building blocks: very limited number
- C1: Carbon
- C2: Carbon
- C3: Fats, fatty acids, polyketides
- C4: Aromatic amino acids, phenylpropanoids
- C5: Terpenoids, steroids
- C6: Alkaloids
The building blocks: source and destination
- Shikimate route: aromatic amino acids, alkaloids
- Acetate route: simple carbon, fats/fatty acids/polyketides/flavonoids/steroids
- MVA/MEP route: isoprene units
- Acetate route-Krebs cycle: peptides/alkaloids
Assembly mechanisms:
- Alkylation: C-C (nucleophilic/electrophilic substitution/addition)
- Wagner-Meerwein rearrangements
- Aldol reaction / Claisen reaction: C-C
- Iminie formation / Mannich reaction: C-N
- Amino acids and transamination
- Decarboxylation
- Oxidation / reduction: C-C > C=C or C-OH > C=O
- Phenolic oxidative coupling C-C
- Halogenation reaction
- Glycosylation
Cofactors: compounds required for an enzyme’s activity to increase rate of a chemical reaction
- Prosthetic group: strong (covalently) bonded organic molecule, no protein
- Coenzyme (co-substrate): small organic substances, not covalent
e.g. NAD+, NADH, FAD, FADH2, ATP, ADP, CoA
Biosynthetic research: studying the sequence of reactions (=metabolic flux) and characterize the
enzymes in vivo. Nowadays, the intermediate molecules and enzymes can be studied.
Isotopic studies: isotopically labelled compound (precursor) > organism > produced metabolite >
isolation, purification, degradation, analysed > detect presence of isotope.
