Role of Methionine in Cephalosporin Synthesis

Abstract

Methionine has an almost unique stimulatory effect on biosynthesis of cephalosporins (by Cephalosporium acremonium ). No other sulfur-containing compound tested, except dl -methionine- dl -sulfoxide, replaced methionine. dl -Methionine stimulated the synthesis of cephalosporins when added after the growth phase. The utilization of inorganic sulfate was repressed by methionine. Experiments with l -methionine- S 35 showed that essentially all the sulfur in the cephalosporins was derived from methionine. Sulfur-labeled compounds found in the soluble pool from cells grown with methionine- S 35 were methionine, homocysteine, taurine, cystathionine, cysteic acid, glutathionine, and cysteine. dl -Serine- 3-C 14 was incorporated into the antibiotics, and its utilization was stimulated by methionine. l -Cysteine had a sparing effect on the incorporation of methionine- S 35 and serine- C 14 into the antibiotics. The data are consistent with the hypothesis that a cystathionine-mediated pathway is operative in the transfer of sulfur between methionine and cysteine.