Gene Interactions Affecting Methionine Biosynthesis and the Response to S-methylcysteine by Mutants of Neurospora crassa

SUMMARY: Two non-allelic suppressors have been isolated which suppress non-allelic, leaky, methionine-requiring mutants blocked either between cysteine and cystathionine or between cystathionine and homocysteine. Strains carrying either suppressor gene in the presence of the me + allele were stimulated by either cysteine or methionine, whereas the suppressed methionine-requiring mutants (me su) although stimulated by methionine were inhibited by cysteine. S-methylcysteine supported the growth of leaky methionine-requiring mutants when it was present as the sole sulphur source and it also stimulated the growth of suppressed methionine-requiring mutants inhibited by cysteine. Sulphate or cysteine inhibited the growth response of certain methionine-requiring mutants to S-methylcysteine. The incorporation of radioactive sulphate into protein methionine was inhibited to a greater extent by S-methylcysteine than was its incorporation into protein cysteine. The results suggest that the sulphur of S-methylcysteine is converted to methionine without prior conversion to cysteine and that the suppressors act by retarding the formation of an inhibitor which accumulates as a result of the primary mutation to methionine requirement.