The chemistry division presents several themes within the unit
Generalizing and improving the use of enhanced bioluminescent reporting systems
One of our research projects is focused on the study of bioluminescent reporting systems made of a luciferin/luciferase pair. As depicted coelenterazine is the substrate of a whole array of luciferases of marine origin and its catalyzed oxidative decarboxylation leads to the production of coelenteramide as well as a blue photon, the most visible color undersea. Our previous work has led to a large-scale process to synthetize enhanced analogs of coelenterazine, notably the O-acetylated luciferins hikarazine-103 and 108. Their availability was a key factor in the successful design of Luciferase-Linked ImmunoSorbent Assays (LuLISA) which were, for instance, used to monitor the COVID-19 pandemic in France. To further understand the mechanism of this photon production, we also designed azacoelenterazine as a non-oxidizable NMR and X-ray probe for structural studies of coelenterazine-using luciferases. This probe actually led to fruitful international collaborations with research groups based in Japan, Czech Republic as well as Denmark.
Further research is currently focusing on structure-based studies to tackle the multiparameter issues of identifying and designing improved luciferins as well as the corresponding luciferases. In collaboration with research groups across the world we are thus working on the design and synthesis of luciferins or luciferin-like probes specifically adapted to their research.
Finally, we have also initiated a project aiming at the identification and cloning of the luciferase of the Periphylla periphylla jellyfish. This is ac quite luciferase and it is also using coelenterazine. It was originally studied by Osamu Shimomura but it remains a rather tough challenge even for modern biological tools.
Anna, F.; Goyard, S.; Lalanne, A. I.; Nevo, F.; Gransagne, M.; Souque, P.; Louis, D.; Gillon, V.; Turbiez, I.; Bidard, F. C.; Gobillion, A.; Savignoni, A.; Guillot-Delost, M.; Dejardin, F.; Dufour, E.; Petres, S.; Richard-Le Goff, O.; Choucha, Z.; Helynck, O.; Janin, Y. L.; Escriou, N.; Charneau, P.; Perez, F.; Rose, T.; Lantz, O. High seroprevalence but short-lived immune response to SARS-CoV-2 infection in Paris. Eur. J. Immunol. 2021, 51, 180-190.
Takatsu, K.; Kobayashi, N.; Wu, N.; Janin, Y.L.; Yamazaki, T.; Kuroda, Y., Biophysical analysis of Gaussia Luciferase bioluminescence mechanisms using a non-oxidizable coelenterazine. Biochim. Biophys. Acta Proteins Proteom. 2023, 3, 100068.
Schenkmayerova, A.; Toul, M.; Pluskal, D.; Baatallah, R.; Gagnot, G.; Pinto, G. P.; Santana, V. T.; Stuchla, M.; Neugebauer, P.; Chaiyen, P.; Damborsky, J.; Bednar, D.; Janin, Y.L.; Prokop, Z.; Marek, M., Catalytic mechanism for Renilla-type bioluminescence. Nat. Catal. 2023, 6, 23-38.
Coutant, E.P.; Gagnot, G.; Hervin, V.O.; Baatallah, R.; Goyard, S.; Jacob, Y.; Rose, T.; Janin, Y.L., Bioluminescence Profiling of NanoKAZ/NanoLuc Luciferase Using a Chemical Library of Coelenterazine Analogues. Chem. Eur. J. 2020, 26, 948-958.
Coutant, E. P.; Goyard, S.; Hervin, V.O.; Gagnot, G.; Baatallah, R.; Rose, T.; Jacob, Y.; Janin, Y.L., Gram-scale synthesis of luciferins derived from coelenterazine and original insights in their bioluminescence properties. Org. Biomol. Chem. 2019, 17, 3709-3713.
Coutant, E. P.; Janin, Y. L. Synthetic routes to coelenterazine and other imidazo[1,2-a]pyrazine-3-one luciferins, essential tools for bioluminescence-based investigations. Chem. Eur. J. 2015, 21, 17158-17171.