Formylmethionine

Formylmethionine, usually written fMet in bacterial initiation, is methionine whose amino group bears a formyl group, $-\mathrm{C}(=\mathrm{O})\mathrm{H}$. The nitrogen modification makes an amide; it does not replace the sulfur-containing side chain. The free neutral L-form has molecular formula ${\mathrm{C}}_6{\mathrm{H}}_{11}\mathrm{N}{\mathrm{O}}_3\mathrm{S}$.^[ref]

In canonical bacterial initiation, methionine is first attached to an initiator transfer RNA and then formylated on that carrier. Bacterial initiation factor IF2 recognizes the formylated end during assembly at the ribosomal P site. Free formylmethionine, its tRNA-bound form and the initiating residue in a peptide are different chemical states.^[ref]

An original atom balance clarifies the modification. Replacing one amino-nitrogen hydrogen in free methionine, ${\mathrm{C}}_5{\mathrm{H}}_{11}\mathrm{N}{\mathrm{O}}_2\mathrm{S}$, by $\mathrm{CHO}$ gives a net addition of $\mathrm{CO}$ and hence ${\mathrm{C}}_6{\mathrm{H}}_{11}\mathrm{N}{\mathrm{O}}_3\mathrm{S}$. The free-compound formula does not include the transfer RNA or account for its ester linkage.

Formylation alone is not a complete initiation signal. In a primary experiment, anticodon-stem variants of an Escherichia coli initiator were purified, aminoacylated and formylated. Some retained IF2 binding but lost efficient P-site binding and initiation. The carrier's RNA structure therefore contributes recognition information beyond its attached formylmethionine.^[ref]