Strain selection,medium development and scale-up of toyocamycin production by streptomyces chrestomyceticus

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.List of Symbols 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 g/(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 g/cm³ Toyocamycin concentration - TNP Tricyclic nucleoside phosphate