The physiology of erythromycin biosynthesis in cyclic fed batch culture.

Antibiotic production in Saccharopolyspora erythraea was significantly enhanced in cyclic fed batch culture (c.f.b.c) compared to batch culture, whereas chemostat culture resulted in reduced production. C.f.b.c. allowed the specific growth rate to be varied, with time, according to an asymptotically decreasing trajectory without the necessity for nutrient exhaustion. It was, therefore, possible to increase productivity by increasing the growth-limiting substrate concentration. It was necessary to apply the c.f.b.c. regime to early-exponential-phase cultures in order to obtain a stable, nutrient-limited, c.f.b.c. The antibiotic production rate during any c.f.b.c. cycle was dependent on the relationship between the specific growth rate at the time and the growth rate at the start of the cycle.