Cephalosporium 발효시 균체의 형태학적 측면을 고려한 수학적 모델링 및 유가식 배양에의 응용

Mathematical Modeling with Cell Morphology and Its Application to Fed-batch Culture in Cephalosporium Fermentation

Cephalosporium 배양시 균체의 형태학적 측면을 고려한 cephalosporin C 생합성에 대한 모델식을 제안하였다. 제한기질로 glucose와 methionine을 고려한 double-substrate 모델을 설정하였는데 여기서 glucose는 균체의 증식 정도를, methionine은 균체의 증식속도를 제어하게 된다. Cephalosporin C의 생산은 균체의 형태학적 분화와 밀접한 관계가 있다. 한편 cephalosporin C의 생산성을 증대시키기 위해 모델식을 유가식 배양에 응용하였다.

A kinetic model incorporating cell morphology in cephalosporin C biosynthesis by Cephalosporium amemoniurn was developed. The double-substrate Double-substrate kinetic model was used to describe cell growth. Methionine controlled the rate of growth while glucose ultimately controlled the extent of growth. The changes in specific product formation rate were associated with morphologenesis, especially cell differentiation. To increase the productivity of cephalosporin C, the proposed model equations were applied to a fed-batch culture. The algorithm to optimize the fed-batch culture consists of two steps; cell growth was maximized in the growth phase and then cephalosporin C production was maximized in the production phase. The increase of about 33% in the cephalosporin C titre was obtained by the optimal feeding scheduling in comparison with that of batch culture.