Shen Y Q, Heim J, Solomon N A, Wolfe S, Demain A L
J Antibiot (Tokyo). 1984 May;37(5):503-11. doi: 10.7164/antibiotics.37.503.
A variety of inorganic and organic nitrogen sources were added to fermentation media to determine their regulatory effects on the production of beta-lactam antibiotics by Cephalosporium acremonium. (NH4)2SO4 at concentrations higher than 100 mM (1.3%) strongly inhibited beta-lactam production. L-Asparagine and L-arginine proved to be the best nitrogen 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 tribasic magnesium phosphate [Mg3(PO4)2 X 8H2O] to the (NH4)2SO4-containing medium stimulated beta-lactam production markedly and ammonium repression of the ring-expansion enzyme was reversed. It appears that the ring-expansion step is a very sensitive part of beta-lactam biosynthesis in C. acremonium with respect to nitrogen source repression. Other enzymes may also be sensitive in view of the fact that nitrogen source derepression not only led to increases in cephalosporin C but, to a lesser extent, penicillin N and total beta-lactam titers.
向发酵培养基中添加了多种无机和有机氮源，以确定它们对顶头孢霉生产β-内酰胺抗生素的调节作用。浓度高于100 mM（1.3%）的硫酸铵强烈抑制β-内酰胺的产生。L-天冬酰胺和L-精氨酸被证明是测试的用于β-内酰胺生产的最佳氮源。天冬酰胺的最佳浓度为1.2%。更高的浓度会导致氨积累、pH值升高和生长速率降低。向含硫酸铵的培养基中添加磷酸三镁[Mg3(PO4)2·8H2O]可显著刺激β-内酰胺的产生，并且环扩张酶的铵抑制作用被逆转。就氮源抑制而言，环扩张步骤似乎是顶头孢霉中β-内酰胺生物合成非常敏感的部分。鉴于氮源去阻遏不仅导致头孢菌素C增加，而且在较小程度上导致青霉素N和总β-内酰胺效价增加，其他酶可能也很敏感。
