Unraveling the methionine-cephalosporin puzzle in Acremonium chrysogenum

Abstract

Methionine has long been known as the major stimulant of the formation of cephalosporin C in Acremonium chrysogenum. Enzymatic and genetic studies of methionine have revealed that it induces four of the enzymes of cephalosporin-C biosynthesis at the level of transcription. It is also converted to cysteine, one of three precursors of cephalosporin C, by cystathionine-gamma-lyase. The main effect of methionine on cephalosporin production results from its regulatory role, which can be duplicated by the non-sulfur analog norleucine. Eliminating cystathionine-gamma-lyase prevents the enhancing precursor effect of methionine on cephalosporin-C production, and cystathionine-gamma-lyase overproduction in moderate doses increases cephalosporin-C formation.