formylmethionine

Formylmethionine, often abbreviated fMet, is the N-formyl derivative of the amino acid methionine. In formylmethionine the amino group of methionine is formylated, producing N-formylmethionine. This modification is biologically important because many organisms initiate protein synthesis with formylated methionine.

In bacteria and in the organelles of eukaryotes that resemble bacterial machinery (mitochondria and chloroplasts), initiation uses a specialized initiator tRNA carrying formylmethionine (tRNAfMet). Met-tRNAfMet is first charged with methionine and then the formyl group is transferred by the enzyme methionyl-tRNA transformylase from formyl-tetrahydrofolate to the amino group, producing fMet-tRNAfMet. This initiator tRNA is selectively recognized by the ribosome and initiation factors to start translation at start codons, typically AUG, though some bacteria may use alternative start signals.

After initiation, the formyl group is usually removed by peptide deformylase, and the initiating methionine can subsequently be removed by methionine aminopeptidase, yielding a mature protein with a non-formylated N-terminus. Thus, the formyl group generally serves a role in initiation and does not persist in most mature cytosolic proteins.

Formylmethionine also has immunological and diagnostic relevance. N-formylated peptides released by bacteria act as chemoattractants for phagocytic cells via formyl peptide receptors, contributing to innate immune responses and signaling the presence of bacterial infection.