title: Plant-driven repurposing of the ancient S-adenosylmethionine repair enzyme homocysteine S-methyltransferase.
abstract: Homocysteine S-methyltransferases (HMTs) are widely distributed enzymes that convert homocysteine (Hcy) into methionine (Met) using either S-adenosylmethionine (AdoMet) or the plant secondary product S-methylmethionine (SMM) as methyl donor. AdoMet is chirally and covalently unstable, with racemization of natural (S,S)-AdoMet yielding biologically inactive (R,S)-AdoMet and depurination yielding S-ribosylmethionine (S-ribosylMet). The apparently futile AdoMet-dependent reaction of HMTs was assigned a role in repairing chiral damage to AdoMet in yeast: yeast HMTs strongly prefer (R,S)- to (S,S)-AdoMet and thereby limit (R,S)-AdoMet build-up [Vinci and Clarke (2010) J. Biol. Chem. 285, 20526-20531]. In the present study, we show that bacterial, plant, protistan and animal HMTs likewise prefer (R,S)- over (S,S)-AdoMet, that their ability to use SMM varies greatly and is associated with the likely prevalence of SMM in the environment of the organism and that most HMTs cannot use S-ribosylMet. Taken with results from comparative genomic and phylogenetic analyses, these data imply that (i) the ancestral function of HMTs was (R,S)-AdoMet repair, (ii) the efficient use of SMM reflects the repurposing of HMTs after the evolutionary advent of plants introduced SMM into the biosphere, (iii) this plant-driven repurposing was facile and occurred independently in various lineages, and (iv) HMTs have little importance in S-ribosylMet metabolism.
authors.affiliation: *Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, U.S.A.
authors.forename: Louis M T
authors.initials: LM
authors.lastname: Bradbury
authors.affiliation: *Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, U.S.A.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ziemak
authors.affiliation: †University of California, Davis Genome Center, Davis, CA 95616, U.S.A.
authors.forename: Mona
authors.initials: M
authors.lastname: El Badawi-Sidhu
authors.affiliation: †University of California, Davis Genome Center, Davis, CA 95616, U.S.A.
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
authors.affiliation: *Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, U.S.A.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hanson
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000201:enzymology / Q000235:genetics; D019143:Evolution, Molecular; D050904:Homocysteine S-Methyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008322:Mammals / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010944:Plants / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D012436:S-Adenosylmethionine / Q000378:metabolism*
chemical_list: D010940:Plant Proteins; D012436:S-Adenosylmethionine; D050904:Homocysteine S-Methyltransferase