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

Abstract

The batch productivity (QTM) 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 QTM 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, Tv. 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 Tv maintained in scale-up in geometrically similar vessels was most beneficial for duplication of optimal antibiotic productivity, QTM. Pilot fermentations (120 dm3 scale) were used to determine coefficients of QTM variation from oxygen uptake rate (OUR) and total CO2 evolution data for monitoring of QTM variation during scale-up to the 12,000 dm3 scale. This technique allowed for on-line prediction of antibiotic titer and QTM from fermentor exhaust gas data.