A Tale Of Two Luciferins: Fungal and Earthworm New Bioluminescent Systems.

Bioluminescence, the ability of a living organism to produce light through a chemical reaction, is one of Nature's most amazing phenomena widely spread among marine and terrestrial species. There are various different mechanisms underlying the emission of "cold light", but all involve a small molecule, luciferin, that provides energy for light-generation upon oxidation, and a protein, luciferase, that catalyzes the reaction. Different species often use different proteins and substrates in the process, which suggests that the ability to produce light evolved independently several times throughout evolution. Currently, it is estimated that there are more than 30 different mechanisms of bioluminescence. Even though the chemical foundation underlying the bioluminescence phenomenon is by now generally understood, only a handful of luciferins have been isolated and characterized. Today, the known bioluminescence reactions are used as indispensable analytical tools in various fields of science and technology. A pressing need for new bioluminescent analytical techniques with a wider range of practical applications stimulates the search and chemical studies of new bioluminescent systems. In the past few years two such systems were unraveled: those of the earthworms Fridericia heliota and the higher fungi. The luciferins of these two systems do not share structural similarity with the previously known ones. This Account will survey structure elucidation of the novel luciferins and identification of their mechanisms of action. Fridericia luciferin is a key component of a novel ATP-dependent bioluminescence system. Structural studies were performed on 0.005 mg of natural substance and revealed its unusual extensively modified peptidic nature. Elucidation of Fridericia oxyluciferin revealed that oxidative decarboxylation of a lysine fragment of luciferin supplies energy for light generation, while a fluorescent CompX moiety remains intact and serves as a light emitter. Along with luciferin, a number of its natural analogs were found in the extracts of worm biomass. They occurred to be highly unusual modified peptides comprising a set of amino acids, including threonine, aminobutyric acid, homoarginine, unsymmetrical N,N-dimethylarginine and extensively modified tyrosine. These natural compounds represent a unique peptide chemistry found in terrestrial animals and raise novel questions concerning their biosynthetic origin. Also in this Account we discuss identification of the luciferin of higher fungi 3-hydroxyhispidin which is biosynthesized by oxidation of the precursor hispidin, a known fungal and plant secondary metabolite. Furthermore, it was shown that 3-hydroxyhispidin leads to bioluminescence in extracts from four diverse genera of luminous fungi, thus suggesting a common biochemical mechanism for fungal bioluminescence.