Transformylases

Transformylases are enzymes that catalyze the transfer of a formyl group (CHO) from a donor molecule to an acceptor substrate. This class participates in both nucleotide biosynthesis and protein synthesis, and its members operate in bacteria, archaea, and organelles of eukaryotes. The most studied donors are 10-formyltetrahydrofolate and related one-carbon carriers, which donate formyl groups in a stereospecific manner to various acceptors.

A prominent example is methionyl-tRNA formyltransferase (MTF; EC 2.1.2.9), which formylates the initiator methionyl-tRNA (tRNAfMet) to form formylmethionyl-tRNAiMet, enabling initiation of protein synthesis in bacteria and in some organelles. MTFs are widespread in bacteria and present in plant chloroplasts and many mitochondria; their essentiality varies across taxa.

Another major group comprises glycinamide ribonucleotide transformylases (GAR transformylases; EC 2.1.2.2), which transfer formyl from 10-formyltetrahydrofolate to glycinamide ribonucleotide (GAR) to yield formylglycinamide ribonucleotide (FGAR) during de novo purine biosynthesis. Bacteria encode two related enzymes, PurN and PurT, reflecting alternative strategies to supply the formyl donor.

Transformylase activity is a target for antimicrobial and anticancer strategies because interfering with formyl transfer can block nucleotide synthesis or translation initiation. Inhibitors of MTFs and GAR transformylases have been explored experimentally, with varying levels of success across organisms.

In summary, transformylases are a diverse set of enzymes that drive formyl-transfer reactions in essential cellular pathways, most notably initiating bacterial protein synthesis and purine biosynthesis, through formyl donors such as 10-formyltetrahydrofolate and related substrates.