Repression of .BETA.-lactam production in Cephalosporium acremonium by nitrogen sources.

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Abstract
A variety of inorganic and organic N sources were added to fermentation media to determine their regulatory effects on the production of .beta.-lactam antibiotics by C. acremonium. (NH4)2SO4 at concentrations higher than 100 mM (1.3%) strongly inhibited .beta.-lactam production. L-Asparagine and L-arginine were the best N sources tested for .beta.-lactam production. The optimum concentration of asparagine was 1.2%. Higher concentrations led to NH3 accumulation, increase in pH and lower growth rates. Addition of Mg3(PO4)2 .cntdot. 8H2O to the (NH4)2SO4-containing medium stimulated .beta.-lactam production markedly and ammonium repression of the ring-expansion enzyme was reversed. The ring-expansion step may be a very sensitive part of .beta.-lactam biosynthesis in C. acremonium with respect to N source repression. Other enzymes may also be sensitive in view of the fact that N source depression not only led to increases in cephalosporin C but, to a lesser extent, penicillin N and total .beta.-lactam titers.