Expanding the Repertoire of Flavoenzyme-Based Biocatalysis

The flavin tricyclic conjugated isoalloxazine ring system can undoubtedly be recognized as one of the most versatile cofactor types. Flavin-dependent enzymes display a remarkable wide range of chemical reactions which involve both one- and two-electron transfers and even nonredox reactions. Flavoenzymes and their catalog of reaction types have been exhaustively documented over the past 100 years. However, recent discoveries have unveiled new hidden troves of flavoenzymology. The N5-oxide flavin cofactor was shown to be involved in a new mechanism of oxidizing a substrate. The prenylated flavin cofactor was found to be key in catalyzing carboxylation and decarboxylation reactions. Another atypical flavin cofactor is also discussed: the deazaflavin cofactor F420. Enzymes utilizing this cofactor show great potential as they display activities that are distinct from flavoproteins that use regular flavins. Furthermore, recent findings on the role of the frequently observed covalent flavin-protein linkages reveal how such covalent interactions allow enzymes to be equipped with special catalytic properties. In addition to providing a way to tune the redox potential through covalent tethering the flavin to a protein, the observed bicovalent linkage allows flavoproteins to evolve towards oxidases that deal with rather bulky substrates by virtue of their exceptionally open active sites. The emerging biocatalytic properties of newly discovered flavoenzymes will open up new possibilities for applications in various fields, including biocatalysis, pharmaceuticals, and biotechnology.