Major classes of natural products 1

Question 1

Primary metabolites
1. essential for?
2. common across?
3. involved in?
4. participate in defence (yes/no)?

Answer 1

1. organisms (amino acids, nucleotides, sugars)
2. most organisms
3. growth, reproduction and development
4. no

Question 2

Secondary metabolites
1. Essential for survival (yes/no)?
2. unique to?
3. not involved in?
4. important for?

Answer 2

1. no
2. an organism or a group of organisms
3. growth, reproduction and development
4. defence and give an advantage to the organism

Question 3

In chemistry what do natural products usually refer to?

Answer 3

‘organic’ molecules that are not involved in core metabolism, but which benefit the producing species

Question 4

In chemistry, ‘organic’ molecules are also known as, and why?

Answer 4

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

Question 5

Where do natural products all arise from?

Answer 5

core metabolic pathways

Question 6

Natural products are formed from?

Answer 6

relatively simple precursors

sugars -> carbohydrates, glycosides
amino acids -> peptides, alkaloids
Acyl-CoAs -> fats, esters, lipids, waxes, polyketides
Isopentyl pyrophosphates -> terpene

Question 7

Bonds add to, and examples?

Answer 7

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)

Question 8

Rules of drawing chemical structures
Where does C live?

Answer 8

bends and ends

Question 9

Rules of drawing chemical structures
What chemical element makes C happy?

Answer 9

H, bonds with C

Question 10

How are formulas written?

Answer 10

C H O
with small numbers at the bottom, found by counting each chemical element up in the chemical structure drawing

Question 11

Biosynthetic Gene Cluster (BGC)
What does end of arrow and point of arrow represent in diagram?

Answer 11

end of arrow = start codon
point of arrow = stop codon

Question 12

What occurs with BGC synthase gene (backbone)?

Answer 12

transcribed into mRNA & translated

Question 13

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?

Answer 13

1. acyl CoAs
2. Lovastatin C24H36O5, Nystatin C47H75O17, Erythromycin C37H67O13
3. only carbons, hydrogen and oxygens (could be a terpene)

Question 14

Polyketide Biosynthesis
1. what is polyketide biosynthesis related to?
2. what are polyketide produced by?
3. what is the backbone biosynthesised by?

Answer 14

1. related to fatty acid biosynthesis
2. produced by bacteria, fungi and plants but each organisms have some variations
3. synthase gene (backbone) is synthesised by the polyketide synthase (PKS)

Question 15

Polyketide Biosynthesis
1. what are polyketide synthases, and feature where?
2. they can be?

Answer 15

1. megasynthases and feature many active sites with individual activities (domains)
2. can be modular (mostly in bacteria) or iterative (common in fungi)

Question 16

What is PKS split into?

Answer 16

first arrow (shorter, facing right) = mammalian fatty acids, iterative PKS

second arrow (longer, facing right) = modular PKS

Question 17

Function of the domains in PKS
1. what are the building blocks?
2. what are polyketides made of?

Answer 17

1. acetyl CoA (Starting unit) & Malonyl CoA (Extender unit)
2. polyketide - many ketones

Question 18

Polyketide Biosynthesis - Function of the domains in PKS (1-6)

Answer 18

1. Loading
2. Claisan condensation (2 carbons)
3. Keto Reduction (by KR)
4. Dehydration (by DH) - removal of water and makes double bonds
5. Reduction (by ER)
6. Release (by TE)

continue until correct length achieved - this length is determined by the protein

Question 19

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?

Answer 19

1. modular polyketide
2. add 2 carbons
3. the carbonyl group
4. yes

Question 20

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?

Answer 20

1. iterative polyketide
2. add 2 carbons
3. in each cycle some of the domains may not be active
4. no

more complex

Question 21

Polyketide Biosynthesis
Modular vs iterative

Answer 21

modular system we can predict a product

iterative system the final product is cryptic - programmed

Question 22

Polyketide Biosynthesis
1. what does polyketide synthase responsible for?
2. what do tailoring genes encode for?

Answer 22

1. making the backbone of the molecule
2. for additional chemical modifications

Question 23

Polyketide Biosynthesis
Tailoring genes example?

Answer 23

cryptosporioptide

oxidation
methylation
glycosylation
reduction
dimerization
any many more

Question 24

How to recognise a polyketide derive SM (secondary metabolite)?

Answer 24

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

Question 25

Polyketide function and applications

Answer 25

natural functions:
- toxins
- flower colours
- UV protection
- Signalling molecules

biological activities:
- anticancer
- antitumor
- antibacterial
- insecticides

Question 26

Example for polyketide functio and applications
Strobilurin and its derivatives
Strobilurus tenacellus
(Nofiani et al., 2018)

Answer 26

• antifungal compound effective against plant pathogens
• Strobilurin fungicides are worth $3.4 billion (2015)
• make up 25% of the fungicide market

Question 27

Strobilurin biosynthesis vs chemical synthesis

Answer 27

• less steps
• biosynthesis more selective
• fungal produces higher titres
• no harmful chemicals

THF = dangerous