Gregor, C. et al. Proc. Natl Acad. Sci. USA 116, 26491–26496 (2019).

Bioluminescence from luciferases and their substrate luciferins have found extensive use in biomedical research. In comparison to fluorescent proteins, they are beneficial because they do not need light to deliver signal. However, unlike fluorescent proteins, the most widely used systems are not fully genetically encoded. Recent work from Stefan Hell’s lab revealed the full pathway for luciferin formation in a bacterial system of bioluminescence. Gregor et al. now show that this entire pathway can be expressed in mammalian cells to create cell lines that luminesce without the need for exogenous luciferin. For the best signal, the researchers carried out codon optimization of the relevant genes and tested multiple plasmids in mammalian cells. Their work creates expression systems with signals on par with that of firefly luciferase and has important implications for the future of bioluminescence imaging.