flp

Flp, short for flippase, refers to a site-specific DNA recombinase originally identified in the yeast Saccharomyces cerevisiae. The enzyme recognizes specific DNA sequences called FRTs (FLP Recognition Targets), which are typically 34-base-pair motifs. When two FRT sites are present in a DNA molecule, Flp catalyzes recombination between them, enabling rearrangements of the DNA segment flanked by the sites.

The recombination is directional and depends on the relative orientation of the FRT sites. If the sites are aligned in the same orientation, Flp excises the intervening DNA as a circular molecule, leaving behind a single FRT site. If the sites are inverted relative to each other, the intervening segment is inverted. If the two FRT sites reside on different DNA molecules, translocation or integration can occur. These properties make Flp a versatile tool for genome engineering across a range of organisms.

The Flp–FRT system is widely used for genetic manipulations such as conditional gene knockouts, lineage tracing, and the construction of complex genetic alleles. It is employed in model organisms including Drosophila, mice, plants, and cultured cells. To improve performance in mammalian cells, codon-optimized variants and enhanced versions (for example, FLPo) have been developed, along with inducible forms such as Flp recombinase fused to regulatory domains.

Compared with the Cre–loxP system, Flp–FRT offers an alternative recombination platform with a distinct recognition sequence, enabling parallel or sequential genetic modifications within the same organism. Limitations include variable recombination efficiency across species and potential off-target activity if cryptic FRT-like sequences exist in the genome.