Development of the cephalosporin C fermentation taking into account the instability of cephalosporin C

Summary Cephalosporin C undergoes chemical hydrolysis during fermentation at 25°C at a rate of 0.48% per hour to give increasing amounts of 2-(D-4-amino-4-carboxybutyl)thiazole-4-carboxylic acid (compound X). Although the cephalosporin C titer in a fermentation levels off at 160–170h, the total of C+X rises almost linearly up to 200h. Cells, therefore, biosynthesize cephalosporin C at an almost constant rate up to 200h. This instability greatly influences attempts to improve the cephalosporin strain by genetic manipulation, or the process by alterations in technology.