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Leader: Jean-Loup Faulon.
This research team is developping retro-synthesis methods to design and build new metabolic networks. Retro-synthesis consists of determining a set of exogenous genes, which once inserted into a host organism, produce a target compound. This method is applied to therapeutic product synthesis by bacterial strains.
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Our group is interested in systems and synthetic chemical biology. We develop in silico methods to search and design chemical and biological structures and networks constrained by experimental data. The applications of our work include reaction networks inference, structure activity/property relationships and rational molecular design.
Our project within the institute is to demonstrate that retrosynthesis, a widely used technique in chemistry, can be utilized to engineer chassis organisms such as E. coli to biosynthesize specific target compounds. Retrosynthesis analysis transforms a synthetic target product into precursors, following pathways to commercially available starting materials. The transformations are applied in the reverse direction from the actual synthesis. In the case of metabolic engineering, retrosynthesis consists of applying reversed biotransformations (i.e., reversed enzymes catalyzed reactions) to a target product, following pathways to substrates that are endogenous to a chassis organism. We are applying these techniques to engineer E. coli plasmids in order to construct combinatorial libraries of highest rank heterologous pathways found to produce target compounds. Combinatorial libraries are generated through the use of assembly PCR tested first in vitro, then in vivo. Production of the target metabolite is verified by measuring metabolites concentrations and fluxes. |

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