Abstract
A study of interactions between primary metabolite accumulation and secondary metabolism was conducted in continuous culture on defined media using as a model organism Streptomyces noursei, a producer of nystatin and cycloheximide. Data are presented on biomass yield for cultures limited by carbon, nitrogen, phosphorus, sulphur, magnesium, potassium and iron. A three fold higher yield of biomass on phosphate was found for phosphate-limited cultures and is discussed in relation to storage products and a possible shift from teichoic acid to teichuronic acid incorporation in cell wall polymers. Using the yield data for carbon and nitrogen, two proline based media were designed to provide proline-carbon- and proline-nitrogen-limited conditions. Further media limited by ammonia or amino acid nitrogen were also designed. Chemostat cultures were grown on these media at a number of dilution rates and steady-state readings obtained for a large number of variables. The data presented include antibiotic production, organic acid accumulation, protein release and yields on oxygen, phosphate and sulphate. The most important finding was that the proline- nitrogen-limited cultures divert an increasing percentage of the available resources into nystatin as growth rate increases, resulting in the maximum rate of production coinciding with the maximum specific growth rate. In contrast, the other types of culture show little change or, the more commonly observed tendency to lose biosynthetic capacity with increasing growth rate. Low growth rates in glutamate-nitrogen-limited cultures led to a reduction in nystatin production which could not be reversed by increasing the dilution rate. Carbon and nitrogen balances reflect the distribution of these elements amongst the products of metabolism and provide evidence that nitrogen-limited cultures divert excess carbon into organic acids.