fMet

N-formylmethionine (fMet) is a formylated derivative of the amino acid methionine. The formyl group is attached to the amino group of methionine, producing N-formylmethionine. In cells, formylation is carried out on the initiator methionine bound to its tRNA by the enzyme methionyl-tRNA formyltransferase, using formyl-tetrahydrofolate as the formyl donor.

In many bacteria, and in organelles that originate from ancestral bacteria such as mitochondria and chloroplasts, fMet-tRNAiMet serves as the initiator tRNA for protein synthesis. The initiation complex comprises the small ribosomal subunit, initiation factors (notably IF2, with assistance from IF1 and IF3 in bacteria), and the formylated initiator tRNA at the start codon. The formyl group helps to distinguish the initiator tRNA from elongator tRNAs and stabilizes initiation complex formation.

After a nascent polypeptide is synthesized, the formyl group is typically removed by peptide deformylase, and often the initiating methionine is removed by methionine aminopeptidase, depending on the second amino acid and processing conditions. Cytosolic translation in most eukaryotes does not use fMet; instead, translation begins with methionine that may be retained or removed during maturation.

fMet is a key feature in bacterial translation and in the translated genomes of mitochondria and chloroplasts. It has also been exploited in research and antibiotic development, where enzymes like formyltransferase and peptide deformylase are targets.