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Team:INSA-Lyon/Project/Theory/Project 3
From 2010.igem.org
Project 3
Evolution has been naturally performing synthetic biology for the last thousands years without our knowledge. Evolution combined with mutation and environmental changes has designed and constructed new biological functions and systems not found so far in nature.
This project aims to study how this happened and to use this knowledge to engineer a more evolved structure into a chassis that did not possess it.
We have studied the multi-enzyme Type I Fatty Acid Synthase (FAS I) as a model in this area. This enzyme is indeed peculiar since it is able to catalyze 6 reactions, as shown on the drawing below, extracted from Wikipedia, visualization by Kosi Gramatikoff. This multifunctional polypeptide is not a single enzyme but can be visualized as a hand comprising functional domains and passing the substrates to one another. This 270 kDa heavy chain is approximately 2000 amino acids long and is present amongst mammals and fungi. This type of FAS has been characterized as being Type I (FAS I), in comparison with Type II Fatty Acid Synthase system (FAS II) which use discrete monofunctional enzymes for fatty acid synthesis.
FAS I model, extracted from Wikipedia, visualization by Kosi Gramatikoff.
The organization of those FAS, integrated in FAS I, discrete in FAS II, differ from one another but their mechanisms of elongation and reduction are quite alike. Each separated FAS II enzymes can be associated to its equivalent domain in FAS I.
The evolutionary history of fatty acid synthases is therefore a tremendous source of information which will enrich our understanding of why and how FAS I and FAS II have co-evolved.
When the chain is 16 carbon atoms long, a last step is performed where the Acyl Carrier Protein is removed:
FAS I enzyme is therefore a multifunctional protein catalyzing the reactions of Malonyl and Acetyl Transferase, β Ketoacyl-ACP Synthase, β Ketoacyl-ACP Reductase, 3 Hydroxyacyl-ACP Dehydrase, Enoyl Reductase and Thioesterase, as refered in the table below with their corresponding EC_numbers.
