Bioluminescence is a fascinating phenomenon in which an organism is able to produce light through a chemical reaction. The specifics of the enzyme and substrate involved differ between species, meaning that bioluminescence has evolved independently several times in the history of life. Bioluminescence is used among animals to, for example, lure their prey, find mating partners, or as a warning signal. Interestingly, in many cases, such as the firefly or coelenterates, a similar dioxetanone moiety was found to be responsible for light emission, and this moiety has been extensively studied. However, the luciferin of some other species, such as dinoflagellates, do not have such a moiety, and it is thus important to study them to see if some common patterns can still be found.
Dinoflagellates are responsible for most of the bioluminescence observed in the sea. Lingulodinium polyedrum in particular is a species of dinoflagellates that emits blue-light flashes in response to mechanical stimulation. The emission is triggered by the oxidation of luciferin, an open-chain tetrapyrrole, catalysed by the dinoflagellate luciferase and is known to be pH regulated. The luciferase enzyme is inactive at basic pH and most active under acidic conditions. A proposed mechanism for activation suggests an opening of the helix bundle and of the binding pocket, thus enabling the luciferin to bind to the beta-barrel. The structure of the complex and the mechanism of activation, however, still remain unknown.
The aim of this project is to study the luciferin and luciferase of dinoflagellates using theoretical tools. Preliminary results show that this reaction likely needs acid/base reaction between the luciferin and luciferase to work. We aim to dock the luciferin to the luciferase to find which amino acids are in the vicinity of the luciferin. This involves an extensive molecular dynamics simulation and enhanced sampling methods, as the structure of the protein is only known in its inactive form. Next, quantum chemical calculations and hybrid QM/MM will be performed to find the mechanism. As in most bioluminescence reactions, the luciferin is first oxidised to form the so-called oxyluciferin, which then undergoes the chemiluminescence reaction. One interesting peculiarity of this specific case is that the emitted light matches the fluorescence spectrum of the luciferin while the oxyluciferin itself is not fluorescent. This has led to the hypothesis that the observed light is not emitted during the reaction, but by energy transfer from the reacting oxyluciferin to an another luciferin located nearby. This cannot be answered without a full simulation of the mechanism.