IChO-2025_2.3
Type: Structure Construction
Points: 18
Question: context: Whilst stereochemical control is challenging synthetically, the biological synthesis controls stereochemistry elegantly through an assembly line of various enzymes. The carbon chain is built up through the addition of monomers. These units are connected via a thioester to Coenzyme A (CoA). The functions of the various enzymes and proteins are shown in the table. The first part of the assembly line is shown with blanks. The enzymes are shown in circles and act in the order of the arrow. Draw in the hexagons the structure of the monomer needed by the enzyme AT at each of the points numbered 1-4. Carbon dioxide is released when the monomers are incorporated. The monomers have the following general structure where the R group is anionic. Fill in each circle with the abbreviations of enzyme(s) needed. Write X if no additional enzyme is needed. Complete the rectangles with the structure of the growing molecule attached to the enzyme.
requirement: Identify the building blocks (in hexagons) and the enzymes (in circles) involved in the polyketide synthesis pathway. Also draw the structures (in rectangles) corresponding to each stage of the synthesis.
table: Abbreviation: ACP
Name: Acyl-carrier protein
Function: Carries growing chain between domains
Abbreviation: CoL
Name: CoA-Ligase
Function: Activates a carboxylic acid substrate to be loaded onto the ACP
Abbreviation: AT
Name: Acyltransferase
Function: Selects monomer and transfers to ACP
Abbreviation: KS
Name: Ketosynthase
Function: Accepts growing chain from previous ACP and activates it for Claisen condensation with next monomer-loaded ACP
Abbreviation: KR
Name: Ketoreductase
Function: Reduces carbonyl of a previous monomer to a hydroxyl
Abbreviation: DH
Name: Dehydratase
Function: Forms α, β-unsaturated thioester via elimination on the previous monomer
Abbreviation: ER
Name: Enoylreductase
Function: Reduces α, β-unsaturated thioester to saturated chain on the previous monomer
answer: question_id: building_blocks_and_enzymes
answer: building_blocks: hexagon_1: name: Me Malonyl CoA
structure: Methylmalonyl-CoA
smiles: CC(C(=O)SCoA)C(=O)[O-]
points: 1
hexagon_2: name: Malonyl CoA
structure: Malonyl-CoA
smiles: [O-]C(=O)CC(=O)SCoA
points: 1
hexagon_3: name: Malonyl CoA
structure: Malonyl-CoA (with methyl branch)
smiles: [O-]C(=O)C(C)C(=O)SCoA
points: 1
hexagon_4: name: Malonyl CoA
structure: Malonyl-CoA (with methyl branch)
smiles: [O-]C(=O)C(C)C(=O)SCoA
points: 1
enzymes: circle_module_1: enzymes: KR
DH
ER
description: Ketoreductase, Dehydratase, Enoyl reductase
points: 2
circle_module_2: enzymes: KR
description: Ketoreductase
points: 2
circle_module_3: enzymes: X
description: Unknown or no additional enzyme beyond KS, AT, ACP
points: 2
circle_module_4: enzymes: KR
DH
description: Ketoreductase, Dehydratase
points: 2
structures: rectangle_1: description: Structure after Module 1 processing
features: Thioester attached to enzyme (S bond)
Fully reduced chain (no ketone)
Cyclohexane ring with two OH groups
Saturated carbon chain
smiles: CC(C)CC(O)C1CCC(O)C(O)C1
stereochemistry: Shows specific stereochemistry with wedge/dash bonds
points: 2
rectangle_2: description: Structure after Module 2 processing
features: Thioester attached to enzyme (S bond)
Beta-hydroxy ketone (ketone reduced to OH)
Cyclohexane ring with two OH groups
Extended carbon chain
smiles: CC(C(=O)CC(O)C)CC1CCC(O)C(O)C1
stereochemistry: Shows specific stereochemistry with wedge/dash bonds
points: 2
rectangle_3: description: Structure after Module 3 processing
features: Thioester attached to enzyme (S bond)
Beta-keto ester (ketone not reduced)
Two carbonyl groups present
Two OH groups on cyclohexane ring
Further extended carbon chain
smiles: CC(C(=O)CC(=O)C(C)CC(O)C)CC1CCC(O)C(O)C1
stereochemistry: Shows specific stereochemistry with wedge/dash bonds
points: 2
rectangle_4: description: Structure after Module 4 processing
features: Thioester attached to enzyme (S bond)
Alpha,beta-unsaturated ketone (dehydrated)
Double bond present
Multiple OH groups
Fully extended carbon chain
Cyclohexane ring with two OH groups
smiles: CC(C(=O)C=C(C)C(C(=O)CC(=O)C(C)CC(O)C)C)CC1CCC(O)C(O)C1
stereochemistry: Shows specific stereochemistry with wedge/dash bonds
points: 2
points: total: 18
breakdown: hexagons: 4
enzymes: 8
structures: 8
grading: building_blocks: Hexagons for building blocks are worth 1 pt each. Total = 4 pts
enzymes_and_structures: Circles for enzymes and rectangles for structures worth 2 pts each. Total 14 pts.
partial_credit: No partial credit for this part. The order of the enzymes in the circles is not graded.
error_carried_forward: Error carried forward can be implemented for the structures in the rectangles.