Major classes of natural products 1 Flashcards
Primary metabolites
1. essential for?
2. common across?
3. involved in?
4. participate in defence (yes/no)?
- organisms (amino acids, nucleotides, sugars)
- most organisms
- growth, reproduction and development
- no
Secondary metabolites
1. Essential for survival (yes/no)?
2. unique to?
3. not involved in?
4. important for?
- no
- an organism or a group of organisms
- growth, reproduction and development
- defence and give an advantage to the organism
In chemistry what do natural products usually refer to?
‘organic’ molecules that are not involved in core metabolism, but which benefit the producing species
In chemistry, ‘organic’ molecules are also known as, and why?
secondary metabolites or specialised metabolites
to distinguish from core primary metabolites such as carbohydrates, fats, proteins, DNA, cofactors (vitamins and minerals) and their precursors, which are generally common to all cells
Where do natural products all arise from?
core metabolic pathways
Natural products are formed from?
relatively simple precursors
sugars -> carbohydrates, glycosides
amino acids -> peptides, alkaloids
Acyl-CoAs -> fats, esters, lipids, waxes, polyketides
Isopentyl pyrophosphates -> terpene
Bonds add to, and examples?
first row (periodic table): 2e- (adds to two)
2nd row: 8e- (adds to 8)
H = 1 (needs some more)
C = 4 (needs 4 more)
N = 3 (needs 3)
O = 6 (needs 2)
Rules of drawing chemical structures
Where does C live?
bends and ends
Rules of drawing chemical structures
What chemical element makes C happy?
H, bonds with C
How are formulas written?
C H O
with small numbers at the bottom, found by counting each chemical element up in the chemical structure drawing
Biosynthetic Gene Cluster (BGC)
What does end of arrow and point of arrow represent in diagram?
end of arrow = start codon
point of arrow = stop codon
What occurs with BGC synthase gene (backbone)?
transcribed into mRNA & translated
One of main class of NPs - Polyketide synthase (PKS)
1. building block
2. 3 types?
3. what is their chemical composition most of the time?
- acyl CoAs
- Lovastatin C24H36O5, Nystatin C47H75O17, Erythromycin C37H67O13
- only carbons, hydrogen and oxygens (could be a terpene)
Polyketide Biosynthesis
1. what is polyketide biosynthesis related to?
2. what are polyketide produced by?
3. what is the backbone biosynthesised by?
- related to fatty acid biosynthesis
- produced by bacteria, fungi and plants but each organisms have some variations
- synthase gene (backbone) is synthesised by the polyketide synthase (PKS)
Polyketide Biosynthesis
1. what are polyketide synthases, and feature where?
2. they can be?
- megasynthases and feature many active sites with individual activities (domains)
- can be modular (mostly in bacteria) or iterative (common in fungi)
What is PKS split into?
first arrow (shorter, facing right) = mammalian fatty acids, iterative PKS
second arrow (longer, facing right) = modular PKS
Function of the domains in PKS
1. what are the building blocks?
2. what are polyketides made of?
- acetyl CoA (Starting unit) & Malonyl CoA (Extender unit)
- polyketide - many ketones
Polyketide Biosynthesis - Function of the domains in PKS (1-6)
- Loading
- Claisan condensation (2 carbons)
- Keto Reduction (by KR)
- Dehydration (by DH) - removal of water and makes double bonds
- Reduction (by ER)
- Release (by TE)
continue until correct length achieved - this length is determined by the protein
Polyketide Biosynthesis
Bacteria
1. what type of polyketide?
2. what is added in each step?
3. what does each molecule modify?
4. can we predict the final product?
- modular polyketide
- add 2 carbons
- the carbonyl group
- yes
Polyketide Biosynthesis
Fungi
1. what type of polyketide?
2. what is added in each step?
3. in each cycle what may occur?
4. can we predict the final product?
- iterative polyketide
- add 2 carbons
- in each cycle some of the domains may not be active
- no
more complex
Polyketide Biosynthesis
Modular vs iterative
modular system we can predict a product
iterative system the final product is cryptic - programmed
Polyketide Biosynthesis
1. what does polyketide synthase responsible for?
2. what do tailoring genes encode for?
- making the backbone of the molecule
- for additional chemical modifications
Polyketide Biosynthesis
Tailoring genes example?
cryptosporioptide
oxidation
methylation
glycosylation
reduction
dimerization
any many more
How to recognise a polyketide derive SM (secondary metabolite)?
Pleuromutilin
Penicillin G
Botrydial
Tenuazonic Acid
always have CHO
can have halogen (Br, Cl, etc.)
some rare examples may have nitrogen atoms
common to have aromatic, hydroxy, and alcohol groups
long chains (similar to fatty acids) and double bonds
Polyketide function and applications
natural functions:
- toxins
- flower colours
- UV protection
- Signalling molecules
biological activities:
- anticancer
- antitumor
- antibacterial
- insecticides
Example for polyketide functio and applications
Strobilurin and its derivatives
Strobilurus tenacellus
(Nofiani et al., 2018)
- antifungal compound effective against plant pathogens
- Strobilurin fungicides are worth $3.4 billion (2015)
- make up 25% of the fungicide market
Strobilurin biosynthesis vs chemical synthesis
- less steps
- biosynthesis more selective
- fungal produces higher titres
- no harmful chemicals
THF = dangerous