Enhancing bioluminescent reporting systems

One of our research projects is focused on the study of bioluminescence-based reporting systems which are made of a luciferin and a luciferase. As depicted below, coelenterazine is the substrate of a wide array of marine luciferases and its oxidative decarboxylation leads to the production of coelenteramide along with a blue photon, the most visible color undersea. Our previous work led to a synthetic process to prepare O-acetylated luciferins such as hikarazines-103 and 108   (doi: 10.1039/c9ob00459a; doi: 10.1002/chem.201904844).

Credits

©Yves-Louis JANIN

Their availability was one of the keys for the design of LuLISA (Luciferase-Linked ImmunoSorbent Assays) based assays which turned out to be exceedingly useful to map the COVID-19 pandemic in France (doi: 10.1002/eji.202049058). In order to undertake structure-based studies of the photon production by these systems, we have also designed and synthesized azacoelenterazine, a non-oxidable probe for coelenterazine-using luciferases. This compound led to fruitful collaboration with research groups from Japan, Czech Republic as well as Denmark (doi.org/10.1101/2022.12.05.519101; doi.org/10.1002/cctc.202300745; doi.org/10.1038/s41929-022-00895-z; doi: 10.1016/j.bbadva.2022.100068).

We pursuing our work in order to further identify the many structural parameters providing a strong bioluminescence either due to the luciferin or the luciferase. Accordingly, we are still collaborating with many research groups to design original luciferins or structurally related luciferase probes which should be specifically adapted to their research.

Finally, we have initiated a project aiming at identifying and cloning the Periphylla periphylla luciferase. This coelenterazine-using luciferase appears to provide a bright signal. It was the focus of Osamu Shimomura studies and it remains a challenge even with the help modern biology research tools.