Methionine biosynthesis pathway

The methionine biosynthesis pathway is a series of enzymatic reactions responsible for the de novo production of methionine, a sulfur-containing amino acid essential for protein synthesis and cellular methylation (Source: PubMed, PMID: 24854971). In many bacteria, fungi, and plants, this pathway converts aspartate into methionine through intermediates like homoserine and homocysteine (Source: Wikipedia, Methionine Biosynthesis). Because humans lack the enzymes for de novo methionine synthesis and must obtain it from their diet, the pathway represents a significant opportunity for selective antimicrobial therapy (Source: Journal of Biological Chemistry, 2014). Targeting enzymes such as cystathionine gamma-synthase (MetB) or methionyl-tRNA synthetase (MetG) can lead to the depletion of methionine and S-adenosylmethionine (SAM), effectively halting pathogen growth (Source: PubChem, CID 23658864). SAM is the primary methyl donor in the cell, meaning its depletion impacts DNA, RNA, and protein methylation (Source: NIH, Office of Dietary Supplements). Inhibitors targeting this pathway, such as REP8839, are being researched for their potential to treat infections caused by multidrug-resistant pathogens like Staphylococcus aureus (Source: ClinicalTrials.gov, NCT00441012). However, a major challenge in targeting this pathway is the potential for pathogens to salvage methionine from the host environment, which can bypass the inhibition (Source: Nature Communications, 2019). This pathway's essentiality in pathogens versus its absence in humans makes it a classic example of metabolic targeting in drug discovery.

Other names

De novo methionine biosynthetic pathwayMethionine metabolic pathwayAspartate-derived methionine synthesis

Inhibition of de novo synthesis enzymes (e.g., MetB, MetC) or aminoacyl-tRNA synthetases (MetG), leading to the depletion of methionine and its derivative S-adenosylmethionine, thereby arresting protein translation and epigenetic regulation (Source: PubMed, PMID: 24854971).