Engineering of Prevalent Luciferase–Luciferin Pairs Toward Tunable Light and Applications in the Field of Bioluminescence Imaging

The photon emission mechanisms of two of the most thoroughly studied luciferase–luciferin pairs, which emit distinct hues of light in the presence of different luciferases by employing d-luciferin and coelenterazine as substrates, respectively, were elucidated as far back as the last century. In an attempt to expand the bioluminescent optogenetic toolkit, scientists have achieved excellent results over the past 20 years by engineering luciferase and chemically modifying luciferin. In light of the widespread adoption of caged luciferin and bioluminescence resonance energy transfer strategies in recent years, a significant variety of bioluminescence-induced optogenetic biosensors have been reported that shed light on physiological events and control of signaling pathways. The purpose of this review is to outline the advances in bioluminescent systems engineering and the broader scope of bioluminescence-driven biomedical applications.