On the diversity of F420-dependent oxidoreductases: a sequence- and structure-based classification

The F 420 deazaflavin cofactor is an intriguing molecule as it structurally resembles the canonical flavin cofactor, although biochemically behaves as a nicotinamide cofactor. Since its discovery, numerous enzymes relying on it have been described. The known deazaflavoproteins are taxonomically restricted to Archaea and Bacteria. The biochemistry of the deazaflavoenzymes is diverse and they exhibit some degree of structural variability as well. In this study a thorough sequence and structural homology evolutionary analysis was performed in order to generate an overarching classification of all known F 420 -dependent oxidoreductases. Five different superfamilies are described: Superfamily I, TIM-barrel F 420 -dependent enzymes; Superfamily II, Rossmann fold F 420 -dependent enzymes; Superfamily III, β-roll F 420 -dependent enzymes; Superfamily IV, SH3 barrel F 420 -dependent enzymes and Superfamily V, 3 layer ββα sandwich F 420 -dependent enzymes. This classification aims to be the framework for the identification, the description and the understanding the biochemistry of novel deazaflavoenzymes.