Plant-driven repurposing of the ancient S-adenosylmethionine repair enzyme homocysteine S-methyltransferase

Louis M T Bradbury, Michael J. Ziemak, Mona El Badawi-Sidhu, Oliver Fiehn, Andrew D. Hanson

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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 (SribosylMet). 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 SribosylMet metabolism.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalBiochemical Journal
StatePublished - Oct 15 2014


  • Metabolite damage
  • Methyl metabolism
  • Neofunctionalization
  • S-methylmethionine
  • Vitamin U

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)


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