Continuous production of erythromycin using a carrier-supported mycelium in an air-lift bioreactor

Abstract

The major type of erythromycin produced by Streptomyces erythreus was determined by HPLC and was identified as erythromycin A in given fermentation conditions. A carrier-supported mycellial growth of Streptomyces erythreus was applied to erythromycin fermentation system. The effect of celite size on biomass hold-up and erythromycin production was investigated in flask batch culture using phosphate-limited media. Biomass hold-up was increased with decreased celite size. Maximum biomass-hold-up was 0.12 g-DCW/g-celite (corresponding to 5.9 g/1) in celite size of 210-250 $\mu$m. An in-situ cell separation air-life bioreactor, was designed and operated by continuous production of erythromycin using the bioparticls developed as acarrier-supported mycellial growth. In order to study flow characteristics of novel bioreacter. Mixing time and circulation time were determined and it was found that the presence of draft tube stabilized liquid circulation patterns. In continuous operation to improve the volumetric productivity, phosphate-limited medium was used. At dilution=0.08 $hr^{-1}$, cell growth was increased while the activity of erythromycin production was losed. But stability of erythromycin production was increased at dilution rate=0.008 $hr^{-1}$, that is phosphate feeding rate of 17.7 mg-$KH_2PO_4$/1. day. At this operation 80\% of maximum erythromycin concentratoin was maintained for 420 hrs. Therefore, high erythromycin concentration and stability of erythromycin production were achieved by control of phosphate feeding rate.