Homoserine O-succinyltransferase (MetA)

Homoserine O-succinyltransferase is an essential enzyme that catalyzes the first committed step in the de novo biosynthesis of methionine in bacteria and fungi. It facilitates the chemical reaction where a succinyl group is transferred from succinyl-CoA to L-homoserine, resulting in the formation of O-succinyl-L-homoserine and coenzyme A (UniProt P0A717). This metabolic pathway is critical for the survival of various pathogens, including Mycobacterium tuberculosis and Escherichia coli, particularly in environments where methionine is scarce (PubMed: 25613611). Because humans lack this biosynthetic pathway and must obtain methionine through dietary sources, the enzyme is considered a highly selective target for the development of new antimicrobial agents (PubMed: 30106587). Inhibition of this enzyme leads to methionine starvation, which subsequently halts protein synthesis and prevents bacterial growth. Although there are currently no FDA-approved drugs targeting this enzyme, research into small-molecule inhibitors is active as a strategy to combat multi-drug resistant infections.

Other names

Homoserine succinyltransferaseO-succinylhomoserine synthaseHTSMet1

Inhibition of the first committed step of the methionine biosynthetic pathway, preventing the conversion of L-homoserine to O-succinyl-L-homoserine.