Utilization of Methionine-containing Peptides and Their Derivatives by a Methionine-requiring Auxotroph of Saccharomyces cerevisiae

A number of peptides containing methionine and glycine, such as Met-Met-Gly, Met-Met-Gly-Met, and Met-Met-Gly-Gly, were synthesized by conventional techniques. The growth response of Saccharomyces cerevisiae G1333, a methionine-requiring auxotroph, toward various di-, tri-, and tetrapeptides containing methionine was measured. The yeast mutant utilized and contained peptidase activity toward most of the peptides investigated. Growth curves varied with the amino acid sequence and composition of the peptide substrate. Only three free peptides, Gly-Met-Gly, Met-Met-Gly-Gly, and Met-Met-Met-Gly failed to satisfy the nutritional requirement of strain G1333. A cell-free extract derived from the auxotroph contained peptidases which liberated methionine from these three peptides. Peptides containing COOH-terminal methionine residues were observed to be better growth substrates than those peptides having different amino acid residues at this position. The yeast auxotroph grew on pentamethionine as well as on methyl ester derivatives of (Met)3, (Met)4, and (Met)5. A number of N-acetylated and t-butyloxycarbonyl di- and tri-peptides containing methionine, such as Ac-Met-Met, Ac-Met-Met-Met, Ac-Met-Gly-Met, Boc-Met-Met-Met, and Boc-Gly-Met-Met served as growth substrates. Several peptide derivatives, all containing a COOH-terminal glycine residue, Ac-Met-Gly, Ac-Met-Gly-Gly, Ac-Gly-Met-Gly, and Boc-Met-Met-Gly, failed to support growth of strain G1333. Comparison of the results obtained for the yeast auxotroph with corresponding data for methionine-requiring auxotrophs of E. coli suggests that the ability of both organisms to utilize similar peptide substrates is different.