Abstract
The batch productivity (Q TM) of the production of the nucleoside antibiotic toyocamycin (TM) by Streptomyces chrestomyceticus was increased ten-fold by selection of a UV generated mutant, optimization of pH, increasing incubation temperature from 28 °C to 36 °C, and addition of soy oil. Initial high oxygen transfer rates stimulated Q TM maxima two-fold. Antibiotic production by the mutant strain, U190, however, appeared more shear sensitive than the parent culture FCRF 341 with maximum antibiotic titer being inversely related to impellor tip velocity, T v . For this reason, scale-up could not be done at constant P/V or constant volumetric oxygen transfer. Instead, programming of impeller speed was evaluated in order to maintain optimal impeller tip velocity during scale-up. It was found that a low constant T v maintained in scale-up in geometrically similar vessels was most beneficial for duplication of optimal antibiotic productivity, Q TM. Pilot fermentations (120 dm3 scale) were used to determine coefficients of Q TM variation from oxygen uptake rate (OUR) and total CO2 evolution data for monitoring of Q TM variation during scale-up to the 12,000 dm3 scale. This technique allowed for on-line prediction of antibiotic titer and Q TM from fermentor exhaust gas data.
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Abbreviations
- A :
-
scale constant
- B :
-
shape constant
- C :
-
location of maximum constant
- D m:
-
impeller diameter (m)
- H m:
-
liquid height (m)
- OTR MmolO2·(dm3)−1min−1 :
-
oxygen transfer rate
- OUR MmolO2·(dm3)−1min−1 :
-
oxygen uptake rate
- PCV cm3 :
-
packed cell volume
- P/V watts/dm3 :
-
volumetric power consumption
- Q 1 · min−1 corrected to standard conditions of temperature, pressure:
-
aeration rate
- Q TM μg/(cm3 · h) or kg/(m3 · h):
-
antibiotic productivity
- T m:
-
tank diameter
- T mix s:
-
mixing time
- T v cm · s−1 :
-
impeller tip velocity
- TM μg/cm3 :
-
Toyocamycin concentration
- TNP :
-
Tricyclic nucleoside phosphate
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Flickinger, M.C., Greenstein, M., Bremmon, C. et al. Strain selection, medium development and scale-up of toyocamycin production by streptomyces chrestomyceticus. Bioprocess Engineering 5, 143–153 (1990). https://doi.org/10.1007/BF00369578
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DOI: https://doi.org/10.1007/BF00369578