Optimization of Switching Time from Growth to Product Formation for Maximum Productivity of Recombinant Escherichia coli Fermentation

유전자 재조합 대장균 발효의 최대 생산성을 위한 생육에서 제품 생성으로 전환시기의 최적화

Maximization of productivity of recombinant cell fermentations requires consideration of the inverse relationship between the host cell growth rate and product formation rate. The problem of maximizing a weighted performance index was solved by using optimal control theory for recombinant E. coli fermentation. Concentration of a growth inhibitor was used as a control variable to manipulate the specific growth rate, and consequently the cloned-gene expression rate. Using a simple unstructured model to describe the main characteristics of this system, theoretical analysis showed that the optimal control profile results in an initial high growth rate phase followed by a low growth rate and high product formation rate phase. Numerical calculations were done to determine optimal switching times from the growth to the production stage for two representative cases corresponding to different dependency of the product formation rate on the growth rate. For the case when product formation rate is sensitive to the specific growth rate, the optimized operation yields about 60% increase in the final product concentration compared with a simple batch fermentation.

유전자 조작된 세포 발효공정의 생산수율을 최대화하기 위하여 세포의 성장속도와 제품 생성속도간의 상반관계를 고려하여야 한다. 유전자 조작된 E.coli 발효에 있어, 최적화 이론을 적용하여 두 속도의 가중치를 결정함으로써 생산수율의 최대화를 꾀하였다. 성장저해제의 농도는 비 성장속도를 조절하고 결국 융합된 유전자의 발현 속도를 조절하는 변수로 사용되다. 이런 system의 특성을 위하여 간단한 unstructured model를 사용하였다.