Preferential and high-yield production of a cephamycin C by dissolved oxygen controlled fermentation

Streptomyces sp. P6621-RS1726, a high cephamycin C producing mutant, usually produces cephamycin C together with its precursor, penicillin N, in flask fermentation. The fermentation conditions for selective and high yield production of cephamycin C were investigated using 20-l jar fermentors. As a result, cephamycin C was preferentially produced without penicillin N when the DO level was maintained at least higher than at 10% during the production phase. However, when the agitation speed was too high at the initial stage of the fermentation, the cell growth was inhibited, resulting in suppression of both cephamycin C and penicillin N production, even if the DO was maintained at a high level. Based on these experiments, a computer control system for preferential and high-yield production of cephamycin C was constructed. By using this computer control system, scale-up from a 20-l jar fermentor to a 1,500-l pilot fermentor was carried out with control of the DO level at 20% of saturation during the cephamycin C production phase. As a result, the profile of cephamycin C production in the former was favorably reproduced in the latter.