Lessons Learned from Luminous Luciferins and Latent Luciferases

Compared to the broad palette of fluorescent molecules, there are relatively few structures that are competent to support bioluminescence. Here, we focus on recent advances in the development of luminogenic substrates for firefly luciferase. The scope of this light-emitting chemistry has been found to extend well beyond the natural substrate and to include enzymes incapable of luciferase activity with d-luciferin. The broadening range of luciferin analogues and evolving insight into the bioluminescent reaction offer new opportunities for the construction of powerful optical reporters of use in live cells and animals.