A single-chain and fast-responding light-inducible Cre recombinase as a novel optogenetic switch

Optogenetics enables genome manipulations with high spatiotemporal resolution, opening exciting possibilities for fundamental and applied biological research. Here, we report the development of LiCre, a novel light-inducible Cre recombinase. LiCre is made of a single flavin-containing protein comprising the AsLOV2 photoreceptor domain of Avena sativa fused to a Cre variant carrying destabilizing mutations in its N-terminal and C-terminal domains. LiCre can be activated within minutes of illumination with blue light without the need of additional chemicals. When compared to existing photoactivatable Cre recombinases based on two split units, LiCre displayed faster and stronger activation by light as well as a lower residual activity in the dark. LiCre was efficient both in yeast, where it allowed us to control the production of beta-carotene with light, and human cells. Given its simplicity and performances, LiCre is particularly suited for fundamental and biomedical research, as well as for controlling industrial bioprocesses.

Automated summary

LiCre is a novel light-inducible Cre recombinase, capable of being activated within minutes by blue light with faster and stronger activation effects and lower residual activity in the dark. It shows high efficiency in both yeast and human cells, making it suitable for fundamental research, biomedical research, and industrial bioprocess control.