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The elusive relationship between structure and colour emission in beetle luciferases


In beetles, luciferase enzymes catalyse the conversion of chemical energy into light through bioluminescence. The principles of this process have become a fundamental biotechnological tool that revolutionized biological research. Different beetle species can emit different colours of light, despite using the same substrate and highly homologous luciferases. The chemical reasons for these different colours are hotly debated yet remain unresolved. This Review summarizes the structural, biochemical and spectrochemical data on beetle bioluminescence reported over the past three decades. We identify the factors that govern what colour is emitted by wild-type and mutant luciferases. This topic is controversial, but, in general, we note that green emission requires cationic residues in a specific position near the benzothiazole fragment of the emitting molecule, oxyluciferin. The commonly emitted green–yellow light can be readily changed to red by introducing a variety of individual and multiple mutations. However, complete switching of the emitted light from red to green has not been accomplished and the synergistic effects of combined mutations remain unexplored. The minor colour shifts produced by most known mutations could be important in establishing a ‘mutational catalogue’ to fine-tune emission of beetle luciferases, thereby expanding the scope of their applications.

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Fig. 1: Bioluminescent beetles and the chemical basis for their emission across the visible spectrum.
Fig. 2: Different luciferases operate on the same substrates but emit different wavelengths, as explained in six mechanistic proposals.
Fig. 3: Structures of luciferases from different beetle species.
Fig. 4: Structures of different luciferases bound to reaction products or model reaction intermediates reveal enzymatic changes during bioluminescence.
Fig. 5: Chemical structures of relevant luciferases inhibitors that have been structurally resolved in complex with FLuc.
Fig. 6: Colour-shifting mutations in the structure of a green-emitting luciferase.
Fig. 7: Mutations can affect the colour emitted by naturally green-emitting and naturally red-emitting luciferases.
Fig. 8: Mutations can affect the colour emitted by two naturally green-emitting luciferases.


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We thank New York University Abu Dhabi for financially supporting this work through the Research Enhancement Fund scheme (project “Red- and Green-Emitting Luciferases: Determination of the Color Emission Mechanism”). This work was also supported by the Human Frontier Science Program (project RGY0081/2011, “Excited-State Structure of the Emitter and Color-Tuning Mechanism of the Firefly Bioluminescence”).

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C.C.-L. and P.N. contributed to conceptualization, researching, analysis, discussions, writing the original draft and review/editing of the final draft. N.M.L. contributed to researching, analysis, discussions and review/editing of the final draft. S.S. contributed to analysis, discussions and review/editing of the final draft.

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Correspondence to Panče Naumov.

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Carrasco-López, C., Lui, N.M., Schramm, S. et al. The elusive relationship between structure and colour emission in beetle luciferases. Nat Rev Chem 5, 4–20 (2021).

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