A ROLE FOR ALANINE IN THE AMMONIUM REGULATION OF CEPHALOSPORIN BIOSYNTHESIS IN STREPTOMYCES-CLAVULIGERUS

It is known that excess ammonium supply decreases cephalosporin produc tion and represses cephalosporin synthases. We wondered whether an add itional important effect could be inhibition of synthase action by ala nine. We had previously shown that ammonium addition induced alanine d ehydrogenase and increased intracellular alanine and that alanine coul d inhibit resting cell synthesis of cephalosporins. In the present wor k we confirm the alanine inhibition of antibiotic production by restin g cells. We found L-alanine inhibited three of the four synthases test ed: ACV synthetase, cyclase and expandase; the epimerase was not inhib ited. These data suggest that interference in cephalosporin production by growth in ammonium salts involves synthase inhibition by intracell ular alanine, in addition to the known role of ammonium in synthase re pression.