Feedforward Loops: Evolutionary Conserved Network Motifs Redesigned for Synthetic Biology Applications

Feedforward loops (FFLs) are relatively simple network motifs, made of three interacting genes, that have been found in a large number in E. coli and S. cerevisiae. More recently, they have also been discovered in multicellular eukaryotes. FFLs are evolutionary favored motifs because they enable cells to survive critical environmental conditions. Among the eight types of possible FFLs, the so-called coherent 1 and incoherent 1 FFL are the most abundant. The former carries out a sign-sensitive delay in gene expression; the latter is a pulse generator and a response time accelerator. So far, only few synthetic FFLs have been engineered, either in cell-free systems or in vivo. In this work, we review the main experimental works published on FFLs, with particular focus on novel designs for synthetic FFLs. They are, indeed, quite different from the natural ones that arose during the course of evolution.