Reconstructing the evolutionary history of F420-dependent dehydrogenases

Abstract

During the last decade the number of characterized F420-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 F420-dependent enzymes within the luciferase-like superfamily. By a thorough phylogenetic analysis we inferred that the F420-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 F420-dependent dehydrogenases and the F420-dependent reductases. By such event, the dehydrogenases specialized in generating the reduced deazaflavin cofactor, while the reductases employ the reduced F420 for catalysis. Particularly, we focused on investigating the dehydrogenase subfamily and demonstrated that this group diversified into three types of dehydrogenases: the already known F420-dependent glucose-6-phosphate dehydrogenases, the F420-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 F420-dependent dehydrogenases, their biochemical properties were investigated and compared. We propose an evolutionary path for the emergence and diversification of the TIM-barrel fold F420-dependent dehydrogenases subfamily.

Metabolic pathway rerouting inParaburkholderia rhizoxinicaevolved long-overlooked derivatives of coenzyme F420

“…In recent years, there has been increasing interest in F 420 -dependent enzymes for biocatalytic applications (5, 6, 35, 36). Therefore, the convenient production in E. coli along with the anticipation to discover novel enzymes and regeneration systems specialized for 3PG-F 420 opens intriguing prospects for biocatalysis and metabolic engineering.…”

Cofactor F420-Dependent Enzymes: An Under-Explored Resource for Asymmetric Redox Biocatalysis

“…All structures solved to date from the LLHT family contain a non-prolyl cis peptide in β3 [23][24][25][26]. Recent phylogenetic reconstructions have shown that the F 420 -dependent LLHTs form two clades: the F 420 -dependent reductases and the F 420 -depented dehydrogenases [27]. The F 420 -reductases contain methylenetetrahydromethanopterin reductases (MERs), which catalyze the reversable, ring-opening cleavage of a carbon-nitrogen bond during the biosynthesis of folate in some archaea [28][29][30].…”

“…The first contains F 420 -dependent secondary alcohol dehydrogenases (ADFs) and the hydroxymycolic acid reductase from M. tuberculosis [31]. The second contains the F 420 -dependent glucose-6-phosphate dehydrogenases (FGDs) from Mycobacteria and Rhodococcus, while the third appear to be more general sugar-phosphate dehydrogenases [27]. In contrast to the heterodimeric structure of bacterial luciferase, the F 420 -dependent dehydrogenases form homodimers with the dimer interface burying a relatively large portion of the surface area of the monomers (≈2000 Å 2 , roughly 15% Catalysts 2019, 9, 868 5 of 18 of the total surface area) [24][25][26].…”

Cofactor F₄₂₀-Dependent Enzymes: An Under-Explored Resource for Asymmetric Redox Biocatalysis

“…All structures solved to date from the LLHT family contain a non-prolyl cis peptide in β3 [23][24][25][26]. Recent phylogenetic reconstructions have shown that the F420-dependent LLHTs form two clades: the F420-dependent reductases and the F420-depented dehydrogenases [27]. The F420-reductases contain methylenetetrahydromethanopterin reductases (MERs), which catalyze the reversable, ring-opening cleavage of a carbon-nitrogen bond during the biosynthesis of folate in some archaea [28][29][30].…”

“…The first contains F420dependent secondary alcohol dehydrogenases (ADFs) and the hydroxymycolic acid reductase from M. tuberculosis [31]. The second contains the F420-dependent glucose-6-phosphate dehydrogenases (FGDs) from Mycobacteria and Rhodococcus, while the third appear to be more general sugar-phosphate dehydrogenases [27]. In contrast to the heterodimeric structure of bacterial luciferase the F420-dependent dehydrogenases form homodimers with the dimer interface burying a relatively large portion of the surface area of the monomers (≈ 2000 Å 2 , roughly 15% of the total surface area) [23,25,26].…”