Reconstructing the evolutionary history of F420-dependent dehydrogenases

MARIA LAURA MASCOTTI; KUMAR HEMANT; QUOC-THAI NGUYEN; MAXIMILIANO JURI AYUB; MARCO W. FRAAIJE

Scientific Reports

Nature Publishing Group

Año: 2018

During the last decade the number of characterized F420-dependent enzymes has significantlyincreased. Many of these deazaflavoproteins share a TIM-barrel fold and are structurally relatedto FMN-dependent luciferases and monooxygenases. In this work, we traced the origin andevolutionary history of the F420-dependent enzymes within the luciferase-like superfamily. By athorough phylogenetic analysis we have discovered that the F420-dependent enzymes emergedfrom a FMN-dependent common ancestor. Furthermore, the data show that during evolution, thefamily of deazaflavoproteins split into two well-defined groups of enzymes: the F420-dependentdehydrogenases and the F420-dependent reductases. By such event, the dehydrogenasesspecialized in generating the reduced deazaflavin cofactor, while the reductases employ thereduced F420 for catalysis.Particularly, we focused on investigating the dehydrogenase subfamily and demonstrated thatthis group diversified into three types of dehydrogenases: the already known F420-dependentglucose-6-phosphate dehydrogenases, the F420-dependent alcohol dehydrogenases, and thesugar-6-phosphate dehydrogenases that were identified in this study. By reconstructing andexperimentally characterizing ancestral and extant representatives of F420-dependent dehydrogenasestheir biochemical properties were investigated and compared. By integrating all data,we propose an evolutionary path for the emergence and diversification of the TIM-barrel foldF420-dependent dehydrogenases subfamily.