stochastic modelling of fatty acid biosynthesis elahe radmaneshfar 17th july 2015 rothamsted
TRANSCRIPT
De novo synthesis and biosynthesis of FA
Plastid
Acyl-CoA pool
16:0-CoA18:0-CoA18:1-CoA
FA Synthesis
Endoplasmic Reticulum
LC-PUFA biosynthesis pathway
Kennedy pathway
TAG
Aims of the model
• Developing a predictive mathematical model which: – can help us understand the mechanism of fatty
acid biosynthesis.– Suggest possibility to improve the production of
fatty acid of our interest (Omega-3)
Challenges for building the model
1. Representation of fatty acids
1 1 1 1 1 1 1 1 1 1 1 1 1 1111111111111
0
1111110111111
Elongation and desaturation in this representation
1111111111111 111111111111111 Elongase
1111111111111 1110111111111 Desaturase
Challenges for building the model
2. LC-PUFA (Long Chain Fatty Acid) biosynthesis pathway is not completely understood.
Tomohito Arao T. and Yamada M., Phaeodactylum Tricornutum, Phytochem 1994;35:1177–1181.
Challenges for building the model
2. LC-PUFA (Long Chain Fatty Acid) biosynthesis pathway is not completely understood.
Hamilton M.L., et alMetab Eng. 2014 Mar; 22(100): 3–9.
Model Schematic
Acyl-CoA pool
16:0-CoA18:0-CoA18:1-CoA
Endoplasmic Reticulum
Stochastic modification of
LC-PUFA
18:0 20:0
18:1 20:1
18:2 20:2
18:3 20:3
K influx
K TAG
K e
K d
TAG
Assumptions of the model• There is just one type of elongase and one type
of desaturase in the model. • There is a minimum of 3 carbon distance
between each double bonds.• Desaturation can continue until a molecule is
fully desaturated.• Elongation can happen until the chain length of
an FA reaches maximum chain length, which is set to 20 for now.
• Every three FA molecules can form a TAG molecule.
Time course of FA production
Time evolutionof intermediate fatty acids
Time evolution of TAG fatty acids
Influence of parameters on most probable pathways
Ke /Kd =1, KTAG /Kinflux =0.01 Ke /Kd =0.01, KTAG /Kinflux =1
>20%<20%
Summary
• A stochastic model for biosynthesis of FA has been developed.
• The model demonstrates the influence of different rates (for elongation, desaturation, influx and out flux of a molecule) on the abundance of FA.
• The model can suggest the most probable reactions.
Feature works
• Add 3 (?) different type of desaturase to the model.
• Implement the feedback from TAG/ER(?) to FA pool outside ER.
• A more systematic parameter search.• Search for enzyme parameters via literature
and implement them to the model, maybe adapt the model to prokaryote first?