| Autor: |
Mascotti ML; IMIBIO-SL CONICET, Facultad de Química Bioquímica y Farmacia, Universidad Nacional de San Luis, Ejército de los Andes 950, D5700HHW, San Luis, Argentina., Kumar H; Molecular Enzymology Group, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands., Nguyen QT; Molecular Enzymology Group, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.; Scuola Universitaria Superiore IUSS Pavia, Piazza della Vittoria 15, 27100, Pavia, Italy.; Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City, 41 Dinh Tien Hoang Street, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam., Ayub MJ; IMIBIO-SL CONICET, Facultad de Química Bioquímica y Farmacia, Universidad Nacional de San Luis, Ejército de los Andes 950, D5700HHW, San Luis, Argentina., Fraaije MW; Molecular Enzymology Group, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands. m.w.fraaije@rug.nl. |
| Abstrakt: |
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. |
