Conserved cysteine residues determine substrate specificity in a novel As(III) S-adenosylmethionine methyltransferase from Aspergillus fumigatus

Mol Microbiol. 2017 Apr;104(2):250-259. doi: 10.1111/mmi.13628. Epub 2017 Mar 13.


Methylation of inorganic arsenic is a central process in the organoarsenical biogeochemical cycle. Members of every kingdom have ArsM As(III) S-adenosylmethionine (SAM) methyltransferases that methylates inorganic As(III) into mono- (MAs(III)), di- (DMAs(III)) and tri- (TMAs(III)) methylarsenicals. Every characterized ArsM to date has four conserved cysteine residues. All four cysteines are required for methylation of As(III) to MAs(III), but methylation of MAs(III) to DMAs(III) requires only the two cysteines closest to the C-terminus. Fungi produce volatile and toxic arsines, but the physiological roles of arsenic methylation and the biochemical basis is unknown. Here they demonstrate that most fungal species have ArsM orthologs with only three conserved cysteine residues. The genome of Aspergillus fumigatus has four arsM genes encoding ArsMs with only the second, third and fourth conserved cysteine residues. AfArsM1 methylates MAs(III) but not As(III). Heterologous expression of AfarsM1 in an Escherichia coli conferred resistance to MAs(III) but not As(III). The existence of ArsMs with only three conserved cysteine residues suggest that the ability to methylate MAs(III) may be an evolutionary step toward enzymes capable of methylating As(III), the result of a loss of function mutation in organisms with infrequent exposure to inorganic As(III) or as a resistance mechanism for MAs(III).

MeSH terms

  • Arsenic / metabolism*
  • Arsenicals / metabolism
  • Arsenites / metabolism*
  • Aspergillus fumigatus / metabolism*
  • Conserved Sequence / genetics
  • Cysteine / metabolism
  • Escherichia coli / genetics
  • Fungal Proteins / genetics
  • Methylation
  • Methyltransferases / genetics
  • S-Adenosylmethionine / metabolism
  • Substrate Specificity


  • Arsenicals
  • Arsenites
  • Fungal Proteins
  • S-Adenosylmethionine
  • Methyltransferases
  • Cysteine
  • arsenite
  • Arsenic
  • arsine