Coumarin Luciferins and Mutant Luciferases for Bioluminescence Imaging

Bioluminescence imaging with luciferin-luciferase pairs is a well-established technique for tracking cells and other biological features in animal models. Bioluminescent is a chemical process which does not require an external input for excitation. Bioluminescent imaging is often limited to monitoring single processes in vivo due to the lack of distinguishable probes. Additionally, existing probes typically operate with light in the visible range, which is highly scattered and exhibits poor tissue penetration. 

To address these issues, researchers at UCI and NCI synthesized a new family of coumarin-based luciferins (CouLuc) with complementary mutant enzymes that exhibit far-red to near-infrared emission. This novel shift in emission opens the possibility of pairing with commercial luciferin-luciferase probes to form multicomponent systems. Additionally, far-red to near-infrared emission enables imaging at greater depths in live animals. Based on commercial courmarin precursors, these CouLuc scaffolds can be prepared in a straightforward two-step sequence. The resulting CouLuc with luciferase mutants provides stable substrate-selective luciferases with robust light emission. Overall, these probes are poised to advance the scope of bioluminescence imaging to more complex biological problems.

Researchers at UCI and NCI seek licensing to adopt new applications for this family of far-red to near-infrared emission coumarin-based luciferins (CouLuc) with complementary mutant enzymes.