The Application of Materials Balancing to the Characterization of Sequential Secondary Metabolite Formation in

1733 The high substrate yield factor (0.73 g biomass g glucose-') and low R.Q. (respiratory quotient, i.e. mol C 0 2 evolved per mol O2 consumed) value (0.8) measured during growth-phase batch cultures of Streptomyces cattleya could be rationalized in terms of the fermentation mass balance when the oxidized elemental composition of biomass was considered. R.Q. was also indicative of the sequence of secondary metabolite formation, the value rising in steps as each new product was formed. The period of maximum respiratory activity and phosphate uptake preceded maximum growth and glucose uptake. At the end of the lytic phase, a cyclopentenedione cobalt chelator was produced. The termination of lysis coincided with melanin production. Sequential cephamycin C and thienamycin production then took place. Specific hyphal protein content (per unit RNA) peaked before the production of each new metabolite. Melanin, cephamycin C and thienamycin production were initiated when glucose, ammonia and phosphate, respectively, became growt h-limi ting .