Glutathione synthetase homologs encode α-L-glutamate ligases for methanogenic coenzyme F_(420) and tetrahydrosarcinapterin biosyntheses

摘要

Proteins in the ATP-grasp superfamily of amide bond-forming ligases have evolved to function in a number of unrelated biosyn-thetic pathways. Previously identified homologs encoding gluta-thione synthetase, D-alanine:D-alanine ligase and the bacterial ribosomal protein S6:glutamate ligase have been vertically inherited within certain organismal lineages. Although members of this specificity-diverse superfamily share a common reaction mechanism, the nonoverlapping set of amino acid and peptide substrates recognized by each family provided few clues as to their evolutionary history. Two members of this family have been identified in the hyperthermophilic marine archaeon Methanococcus jann-aschii and shown to catalyze the final reactions in two coenzyme biosynthetic pathways. The MJ0620 (mptN) locus encodes a tetra-hydromethanopterin:α-L-glutamate ligase that forms tetrahydrosarcinapterin, a single carbon-carrying coenzyme. The MJ1001 (cofF) locus encodes a γ-F_(420)-2:α-L-glutamate ligase, which caps the γ-glutamyl tail of the hydride carrier coenzyme F_(420). These two genes share a common ancestor with the ribosomal protein S6:giutamate ligase and a putative α-aminoadipate ligase, defining the first group of ATP-grasp enzymes with a shared amino acid substrate specificity. As in glutathione biosynthesis, two unrelated amino acid ligases catalyze sequential reactions in coenzyme F_(420) polyglutamate formation: a γ-glutamyl ligase adds 1-3 L-glutamate residues and the ATP-grasp-type ligase described here caps the chain with a single α-linked L-glutamate residue. The analogous pathways for glutathione, F_(420), folate, and murein peptide biosyntheses illustrate convergent evolution of nonribosomal peptide biosynthesis through the recruitment of single-step amino acid ligases.