Reconstructing the evolutionary history of F420-dependent dehydrogenases

• Published in: Scientific reports 2018-12, Vol.8 (1), p.1-10, Article 17571
• Main Authors: Mascotti, M. Laura, Kumar, Hemant, Nguyen, Quoc-Thai, Ayub, Maximiliano Juri, Fraaije, Marco W.
• Format: Article
• Language: English
• Subjects: 631/114/663/2009; 631/45/607/1168; 82/80; 82/83; Catalysis; Dehydrogenases; Enzymes; Evolution; Flavin mononucleotide; Humanities and Social Sciences; multidisciplinary; Phylogeny; Science; Science (multidisciplinary); Sugar
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-35590-2

During the last decade the number of characterized F 420 -dependent enzymes has significantly increased. Many of these deazaflavoproteins share a TIM-barrel fold and are structurally related to FMN-dependent luciferases and monooxygenases. In this work, we traced the origin and evolutionary history of the F 420 -dependent enzymes within the luciferase-like superfamily. By a thorough phylogenetic analysis we inferred that the F 420 -dependent enzymes emerged from a FMN-dependent common ancestor. Furthermore, the data show that during evolution, the family of deazaflavoproteins split into two well-defined groups of enzymes: the F 420 -dependent dehydrogenases and the F 420 -dependent reductases. By such event, the dehydrogenases specialized in generating the reduced deazaflavin cofactor, while the reductases employ the reduced F 420 for catalysis. Particularly, we focused on investigating the dehydrogenase subfamily and demonstrated that this group diversified into three types of dehydrogenases: the already known F 420 -dependent glucose-6-phosphate dehydrogenases, the F 420 -dependent alcohol dehydrogenases, and the sugar-6-phosphate dehydrogenases that were identified in this study. By reconstructing and experimentally characterizing ancestral and extant representatives of F 420 -dependent dehydrogenases, their biochemical properties were investigated and compared. We propose an evolutionary path for the emergence and diversification of the TIM-barrel fold F 420 -dependent dehydrogenases subfamily.