Methionine biosynthetic enzyme

Methionine biosynthetic enzymes are a group of proteins responsible for the de novo synthesis of the essential sulfur-containing amino acid methionine in bacteria, fungi, and plants. Because humans lack this biosynthetic pathway and must obtain methionine through their diet, these enzymes represent highly attractive targets for the development of selective antimicrobial and antifungal agents. Key enzymes in this pathway include homoserine O-acetyltransferase (MetA), cystathionine gamma-synthase (MetB), cystathionine beta-lyase (MetC), and methionine synthase (MetH/MetE). Inhibition of these targets leads to methionine starvation, which halts protein synthesis and depletes S-adenosylmethionine (SAM), the primary methyl donor for DNA, RNA, and protein methylation. While several agricultural fungicides like cyprodinil and pyrimethanil are known to target this pathway, clinical drug development is focused on addressing multidrug-resistant pathogens such as Mycobacterium tuberculosis and Aspergillus fumigatus. Research indicates that even in the presence of host methionine, the inhibition of these enzymes can be lethal to pathogens due to metabolic imbalances and the accumulation of toxic intermediates.

Other names

Methionine biosynthetic enzymesMethionine biosynthesis pathway enzymesMet pathway enzymesDe novo methionine biosynthetic enzymes

Inhibition of enzymes within the de novo methionine biosynthetic pathway (such as MetA, MetB, MetC, or MetH/MetE) leads to methionine starvation, which subsequently disrupts protein synthesis and depletes S-adenosylmethionine (SAM), a critical methyl donor for cellular methylation reactions.