Regulation of antibiotic production by iron and oxygen during defined medium fermentations of Streptomyces clavuligerus

SummaryWhen grown in a chemically defined medium, Streptomyces clavuligerus excreted cephamycin C, in addition to other components, throughout most of the growth phase. Ferrous iron and oxygen are required for the biosynthesis of this antibiotic and the concentration of these cofactors was manipulated to maximize cephamycin C production. The iron content of the chemically defined medium was shown to be sub-optimal for antibiotic production and the addition of 130 μg/ml ferrous iron almost doubled the cephamycin C levels to 200 μg/ml. When dissolved oxygen was maintained at saturation levels, only 60–80 μg/ml cephamycin C was produced, and the intermediate penicillin N accumulated to high levels (50 μg/ml). This suggests that the high concentration of dissolved oxygen had a greater effect on the enzymes catalysing the conversion of penicillin N to cephamycin C, than on those involved in the earlier steps of the pathway leading to the formation of penicillin N.

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