Natural Flavins: Occurrence, Role, and Noncanonical Chemistry

Flavoproteins are of key importance to all life on earth for both primary and secondary metabolism. Most flavin-dependent enzymes utilize flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) as redox cofactor for single-electron and hydride transfer as well as oxidation and oxygenation chemistry at the C4a-locus. Over the last decades, several naturally occurring modified flavins, like 8-formylFAD, F420, and prenylFMN, and covalently bound flavins have been discovered, and were found to further expand the toolbox of flavin chemistry, showcasing extraordinary redox potentials and unprecedented chemistry. Recently, also several examples of "exotic" flavin chemistry, such as N5-oxygenation, have been identified in enzymes that utilize the standard flavins FMN and FAD. It shows that nature has been extremely inventive in exploiting flavins and flavin derivatives as cofactors for an exceptionally wide variety of reactions. Future research will reveal whether other, so far hidden, flavoenzyme-catalyzed chemistries exit.