Fermentation experiments to produce validamycins from crude substrates by Streptomyces hygroscopicus were carried out in an external-loop airlift bioreactor (0.0115 m^3 ) with a low ratio of height to diameter of the riser of 2.9 and a ratio of riser to downcomer diameter of 6.6. The influences of gas flow rate and liquid volume on fermentation of validamycins were investigated. Comparisons of validamycin fermentation were made among the external-loop airlift bioreactor, a mechanically stirred tank bioreactor (0.010m^3 ) and shaking flasks. Under the same operation conditions including fermentation medium composition, inoculum ratio and culture temperature, the fermentation time in the external-loop airlift bioreactor (45 h) was shorter than that in the shaking flasks (100 h) and the same as that in the mechanically stirred tank bioreactor. After a total fermentation time of 45 h under optimized operation conditions, average validamycin concentration obtained in the external-loop airlift bioreactor was close to 19630 μg·ml^-1 validamycin concentration in the mechanically stirred tank bioreactor. It was demonstrated that the external-loop airlift bioreactor could substitute for the mechanically stirred tank bioreactor in production of validamycins from crude substrates with dregs by Streptomyces hygroscopicus.
