Increasing oxygen transfer rates (OTR) by increasing impeller speed during the initial period of rapid oxygen uptake and CO2 evolution appeared to increase initial Toyocamycin (TM) production rate but not final antibiotic concentration in ug/cm3 (titer). In fact, final TM antibiotic concentrations ug/cm3 (titer) were significantly reduced at increasing values of impeller tip velocity (Tv) ( Fig. 17). Visible microscopic mycelial damage and reduced titers were observed at the 120 dm3 scale when impeller speed was increased from 420 RPM to 600 RPM.
Because neither dissolved oxygen tension levels nor high impeller speed (and thus high OTR) during the period of maximum TM accumulation (50-150 h) had a positive correlation with final antibiotic titer, it appeared that scale-up based on the values of power/volume (P/V) determined at 120 dm3 scale may not be feasible using constant OTR or constant P/V. This is in contrast to direct correlations of streptomycin productivity based on the values of power/volume (P/V) during Streptomyces sp. fermentations reported by other groups (14, 22, 86, 141, 228, 276).
Because mycelial damage was consistently observed indicating that TM production may be affected by impeller shear, a programmed change in impeller speed was evaluated for both the parent strain FCRF 341 and mutant U190 on both the 1200 and 12,000 dm3 scale to provide initial stimulation of Toyocamycin productivity (QTM) during peak TM productions to minimize mycelial damage. A Tv of 612 cm . s-1 was used for the initial 20 hours of fermentation followed by reduction in Tv to 275 cm . s-1 for the remaining 120 hours of incubation. The parent strain's ability to produce TM appeared to be stimulated by this impeller speed program as anticipated from previous results, while the mutant U190 demonstrated the opposite effect (Fig. 20).
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