Cephamycin production and isopenicillin N synthetase activity in cultures of Streptomyces clavuligerus

Abstract

The relationships between growth, cephamycin production and isopenicillin N synthetase (IPNS) activity in cultures of Streptomyces clavuligerus were examined to establish conditions that optimize the yield and specific activity of the enzyme. Unexpectedly for a secondary metabolic pathway component, IPNS was synthesized preferentially during rapid growth and reached its maximum specific activity in cultures supplied with readily assimilated sources of nitrogen. The activity decreased sharply as cultures entered stationary phase. On the other hand, comparisons of growth and antibiotic production on a range of carbon and nitrogen sources as well as measurements of IPNS activity in chemostat cultures implicated “catabolite repression”, a mechanism usually associated with separation of trophophase and idiophase activities, as an important factor in controlling expression of the secondary metabolic pathway. An explanation for the timing of IPNS biosynthesis is suggested.