Compositions and methods for DNA cytosine carboxymethylation

An isolated genetically modified methyltransferase enzyme having carboxymethyltransferase activity, which catalyzes formation of 5-carboxymethylcytosine employing carboxy-S-adenosyl-L-methionine (CxSAM) as a substrate, said enzyme having an active site motif naturally comprising a polar amino acid residue that is situated adjacent to carbon 5 of a target cytosine present in a nucleic acid of interest, wherein said polar amino acid is substituted with a positively charged amino acid, wherein said enzyme comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:

• 1, and wherein position N374 of SEQ ID NO:
• 1 can be either K or R.