title: A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase.
abstract: COG5598 comprises a large number of proteins related to MttB, the trimethylamine:corrinoid methyltransferase. MttB has a genetically encoded pyrrolysine residue proposed essential for catalysis. MttB is the only known trimethylamine methyltransferase, yet the great majority of members of COG5598 lack pyrrolysine, leaving the activity of these proteins an open question. Here, we describe the function of one of the nonpyrrolysine members of this large protein family. Three nonpyrrolysine MttB homologs are encoded in Desulfitobacterium hafniense, a Gram-positive strict anaerobe present in both the environment and human intestine. D. hafniense was found capable of growth on glycine betaine with electron acceptors such as nitrate or fumarate, producing dimethylglycine and CO2 as products. Examination of the genome revealed genes for tetrahydrofolate-linked oxidation of a methyl group originating from a methylated corrinoid protein, but no obvious means to carry out corrinoid methylation with glycine betaine. DSY3156, encoding one of the nonpyrrolysine MttB homologs, was up-regulated during growth on glycine betaine. The recombinant DSY3156 protein converts glycine betaine and cob(I)alamin to dimethylglycine and methylcobalamin. To our knowledge, DSY3156 is the first glycine betaine:corrinoid methyltransferase described, and a designation of MtgB is proposed. In addition, DSY3157, an adjacently encoded protein, was shown to be a methylcobalamin:tetrahydrofolate methyltransferase and is designated MtgA. Homologs of MtgB are widely distributed, especially in marine bacterioplankton and nitrogen-fixing plant symbionts. They are also found in multiple members of the human microbiome, and may play a beneficial role in trimethylamine homeostasis, which in recent years has been directly tied to human cardiovascular health.
authors.affiliation: Department of Microbiology, Miami University, Oxford, OH 45056;
authors.forename: Tomislav
authors.initials: T
authors.lastname: Ticak
authors.affiliation: Department of Microbiology and.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Kountz
authors.affiliation: Department of Microbiology and.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Girosky
authors.affiliation: Department of Microbiology and Biochemistry Program, The Ohio State University, Columbus, OH 43210; and krzycki.1@osu.edu fergusdj@miamioh.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Krzycki
authors.affiliation: Department of Microbiology, Miami University, Oxford, OH 45056; Miami University Hamilton, Hamilton, OH 45011 krzycki.1@osu.edu fergusdj@miamioh.edu.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Ferguson
mesh_terms: D001622:Betaine / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D045858:Desulfitobacterium / Q000235:genetics / Q000254:growth & development; D005798:Genes, Bacterial; D050938:Glycine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008744:Methylamines / Q000378:metabolism*; D008745:Methylation; D010802:Phylogeny; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D008744:Methylamines; D001622:Betaine; D050938:Glycine N-Methyltransferase; C456839:pyrrolysine; D008239:Lysine; C023336:trimethylamine
keywords: COG5598; Desulfitobacterium hafniense; glycine betaine; l-pyrrolysine; trimethylamine methyltransferase