Methionine.

Abstract

This review focuses on the steps unique to methionine biosynthesis, namely the conversion of homoserine to methionine. The past decade has provided a wealth of information concerning the details of methionine metabolism and the review focuses on providing a comprehensive overview of the field, emphasizing more recent findings. Details of methionine biosynthesis are addressed along with key cellular aspects, including regulation, uptake, utilization, AdoMet, the methyl cycle, and growing evidence that inhibition of methionine biosynthesis occurs under stressful cellular conditions. The first unique step in methionine biosynthesis is catalyzed by the metA gene product, homoserine transsuccinylase (HTS, or homoserine O-succinyltransferase). Recent experiments suggest that transcription of these genes is indeed regulated by MetJ, although the repressor-binding sites have not yet been verified. Methionine also serves as the precursor of S-adenosylmethionine, which is an essential molecule employed in numerous biological processes. S-adenosylhomocysteine is produced as a consequence of the numerous AdoMet-dependent methyl transfer reactions that occur within the cell. In E. coli and Salmonella, this molecule is recycled in two discrete steps to complete the methyl cycle. Cultures challenged by oxidative stress appear to experience a growth limitation that depends on methionine levels. E. coli that are deficient for the manganese and iron superoxide dismutases (the sodA and sodB gene products, respectively) require the addition of methionine or cysteine for aerobic growth. Modulation of methionine levels in response to stressful conditions further increases the complexity of its regulation.