Role of methionine in the regulation of the synthesis of serine hydroxymethyltransferase in Escherichia coli.

The synthesis of serine hydroxymethyltransferase during methionine limitation is different in met A and met B auxotrophs, mutants defective in homocysteine biosynthesis, as compared to met E and met F auxotrophs, mutants which are unable to methylate homocysteine and thus unable to either synthesize methionine de novo or to regenerate it after use via methylation reactions. Methods for the measurement of intracellular concentrations of sulfur-containing amino acids and nucleosides were developed and applied to cultures of the methionine auxotrophs. No definitive correlation between the absolute intracellular concentration of any single metabolite and the rate of serine hydroxymethyltransferase synthesis was found. However, a high correlation (0.92) was found with the ratio of homocysteine to S-adenosylmethionine, with the rate of enzyme synthesis being a hyperbolic function of the ratio. This is consistent with homocysteine acting as an inducer and S-adenosylmethionine as a corepressor of serine hydroxymethyltransferase synthesis with high affinity for a repressor molecule. This correlation holds only during methionine limitation, and was not observed during glucose limitation or in unrestricted cultures with added adenosine.