LARGE-SCALE CULTURE OF THE MILDIOMYCIN PR ODUCER STREPTOVERTICILLIUM-RIMOFACIENS

The conditions required to scale up the production of mildiomycin usin g Streptoverticillium rimofaciens from a shaking flask to a large-size stirred fermenter were investigated. In a 200-ml shaking-flask cultur e, mycelial pellets ranging from 0.3 to 0.7 mm in diameter made up abo ut 70% of the total, but in a 5-l jar fermenter culture, pellets in th is size range comprised only 8%. In the jar fermenter culture, ammoniu m nitrogen assimilation was reduced, followed by a decrease in mildiom ycin production. The features of the jar fermenter culture were reprod uced in the shaking flask by the addition of a glass bead (phi, 4.9 mm ) to the culture. Using a shaking flask containing a glass bead, inorg anic phosphate feeding was found very effective in stimulating ammoniu m nitrogen assimilation and mildiomycin production. With inorganic pho sphate feeding, the optimal agitation aeration conditions for the cult ure were established using a 5-l jar fermenter. By controlling both th e agitation speed and dissolved oxygen level, production was scaled up from a 5-l jar fermenter to 200-l, 6-m(3), and 120-m(3) fermenters. T he profile of mildiomycin production in the jar fermenter was favorabl y reproduced in the larger fermenters.