The major type of erythromycin produced by $\underline{Streptomyces}$ $\underline{erythreus}$ was determined by HPLC and was identified as erythromycin A in given fermentation conditions.
A carrier-supported mycellial growth of $\underline{Streptomyces}$ $\underline{erythreus}$ 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 5.9g/1) in celite size of 210-250μm.
An in-situ cell separation air-life bioreactor, was designed and operated by continuous production of erythromycin using the bioparticles 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 $mg-KH_2PO_4/l·day$. At this operation 80% of maximum erythromycin concentration was maintained for 420 hrs. Therefore, high erythromycin concentration and stability of erythromycin production were achieved by control of phosphate feeding rate.
$\underline{Streptomyces} \underline{erythreus}$ 의 포자를 다공성 담체물질인 celite에 흡착, 배양시킴으로써 균사를 고정화시켜 얻어진 균사 증식 담체를 공기기거식 생물반응기(air-lift bioreactor)내에서의 에리스로마이신 생산에 이용하였다. 생성되는 에리스로마이신의 종류에는 여러가지가 있으나 HPLC 로 분석한 결과 에리스로마이신 A 형태가 주된 생성물임을 알았다. 또한 고정화에 이용되는 celite의 크기가 작아질수록 고정화 균체량 (biomass hold-up) 은 증가함을 알 수 있었다. 연속조업을 가능케 함으로써, 생산성을 높히기위해 생물반응기내에서 균사 증식 담체와 배양액의 분리가 가능한 in-situ cell separation 형태의 공기기거식 생물반응기가 제작되어졌다. 이 생물반응기 내에서 유체흐름의 특성을 살펴본 결과 draft tube의 존재가 유체의 흐름을 안정화 시키는것을 알았다. 장기간의 연속 조업에는 에리스로마이신의 생성 활성을 증대시키기 위해 인산 제한 배지가 사용되어졌으며 희석율을 낮출수록, 즉 인산공급속도를 낮춤으로써 에리스로마이신 생성 활성이 오랫동안 유지됨을 보여주고 있으며 고정화 세포의 회분식 배양에서 보다 생산성이 약 3 배 증가되었다. 그리고 인산 공급 속도가 $17.7mg-KH_2PO_4/l$·day일 때 에리스로마이신 농도는 최대농도의 80 % 이상이 약 20 일간 유지되었다.
