Lysine 2,3-Aminomutase and a Newly Discovered Glutamate 2,3-Aminomutase Produce β-Amino Acids Involved in Salt Tolerance in Methanogenic Archaea.

Many methanogenic archaea synthesize β-amino acids as osmolytes that allow survival in high salinity environments. Here, we investigated the radical S -adenosylmethionine (SAM) aminomutases involved in the biosynthesis of N ε -acetyl-β-lysine and β-glutamate in Methanococcus maripaludis C7. Lysine 2,3-aminomutase (KAM), encoded by MmarC7_0106, was overexpressed and purified from Escherichia coli, followed by biochemical characterization. In the presence of l-lysine, SAM, and dithionite, this archaeal KAM had a k cat = 14.3 s -1 and a K m = 19.2 mM. The product was shown to be 3( S )-β-lysine, which is like the well-characterized Clostridium KAM as opposed to the E. coli KAM that produces 3( R )-β-lysine. We further describe the function of MmarC7_1783, a putative radical SAM aminomutase with a ∼160 amino acid extension at its N-terminus. Bioinformatic analysis of the possible substrate-binding residues suggested a function as glutamate 2,3-aminomutase, which was confirmed here through heterologous expression in a methanogen followed by detection of β-glutamate in cell extracts. β-Glutamate has been known to serve as an osmolyte in select methanogens for a long time, but its biosynthetic origin remained unknown until now. Thus, this study defines the biosynthetic routes for β-lysine and β-glutamate in M. maripaludis and expands the importance and diversity of radical SAM enzymes in all domains of life.