Production of penicillin in a fluidized-bed bioreactor using a carrier-supported mycelial growth

Abstract

A carrier-supported mycelial growth of Penicillium chrysogenum was applied to penicillin fermentation system, using celite as a carrier material. A fluidizedbed fer-mentor was designed and operated for penicillin production using the bioparticles developed as a carrier-supported mycelial growth. The mode of a repeated fed-batch operation was carried out in a fermentor. In rich medium, the overgrowth of free mycelia and bioparticles caused poor mixing and the fermentor operation quite difficult. To solve this problem, the limitation of medium was tried. The limitation of nitrogen or phosphate resulted in higher specific production rate and poor mycelial growth during fermentation. The morpology of bioparticles showed smooth compact bioparticles in phosphate limited medium as compared with fluffy loose bioparticles in nitrogen limited medium that made long operation difficult. The optimal phosphate feeding rate was determined to be 0.02\% corn steep liquor per day(corresponding to 10mg-$KH_2PO_4$/liter/day). At this phosphate limited condition, the bioparticle size could be successfully controlled. Penicillin production was also observed to be maintained at a high level (about 80\% of the maximum) for at least one month. The overall volumetric productivity of penicillin was calculated to be improved by three or four times comparing to that encountered with the conventional batch fermentation by dispersed mycelial growth.