5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase (MetE)

5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase, commonly known as cobalamin-independent methionine synthase (MetE), is a zinc-dependent enzyme that catalyzes the final step of de novo methionine biosynthesis. It facilitates the transfer of a methyl group from 5-methyltetrahydrofolate to L-homocysteine to produce L-methionine and tetrahydrofolate. Unlike the human methionine synthase (MTR), MetE does not require vitamin B12 (cobalamin) as a cofactor and specifically utilizes polyglutamated folate substrates. This enzyme is found in bacteria, plants, and fungi but is notably absent in mammals, making it a significant target for the development of novel antimicrobial and antifungal agents. Inhibition of MetE leads to methionine starvation and impaired protein synthesis in pathogens, providing a selective therapeutic window with minimal risk of cross-reactivity in human hosts.

Other names

Cobalamin-independent methionine synthaseVitamin-B12-independent methionine synthaseMetETetrahydropteroyltriglutamate methyltransferaseHomocysteine methylaseMethyltetrahydropteroylpolyglutamate:homocysteine methyltransferase5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase

Inhibition of methionine biosynthesis leading to amino acid starvation and suppression of protein synthesis in pathogens.