Design of new pyoverdine analogs using synthetic biology approaches – PYANO

One of the major challenge of the century, the fight against antimicrobial resistance, can be addressed using the emerging field of synthetic biology. One strategy to eradicate multidrug resistant bacteria is to design new antibiotic vectors, more specific and efficient. Siderophores (small peptide chelators produced, secreted and taken up by bacteria to get access to iron) are used as antibiotic vectors. The antibiotic attached to the siderophore uses the ferri-siderophore transport system to enter the cell and reach its target. This is a promising strategy to treat infection with P. aeruginosa, a strain that synthesize the siderophore pyoverdine. In this project, I propose to modify the pyoverdine biosynthesis pathway in P. aeruginosa using enzymatic and metabolic engineering, in order to produce in vivo-functionalized pyoverdine. Antibiotic-pyoverdine hemisynthetic conjugates will be easily obtained by bioconjugation, an unprecedented approach in this domain.