Combinatorial biosynthesis of backbone cyclic peptides in Escherichia coli. Toward the selection of new drugs

Patrice Soumillion (UCL)

Date and place: Wednesday May, 12th 12:30 pm at A3 (B7b)

Split inteins can perform backbone cyclization of oligo- and poly-peptides by an autocatalytic splicing reaction at the protein level. They are used for the creation of ribosomally encoded libraries of so-called "non natural natural" products that can be considered as new mines in drug discovery. After evaluating the sequence determinants that are required for the efficient splicing of a cyanobacterial mini-intein, we have build combinatorial libraries of cyclic hexa-, hepta- and octa-peptides in E.coli. Strategies were also developed for biosynthesizing the peptides in the bacterial periplasm and for their extracellular secretion therefore allowing to address formerly inaccessible targets. Innovative approaches for identifying peptides acting as antibiotics or inhibitors of specific membrane proteins are currently under development.