Recombinant Escherichia coli BL21 was used to produce human-like collagen in fed-batch culture. After building and analyzing the kinetic models of fed-batch cultures, the maximum specific growth rate, Yx/s and Yp/s were 0.411 h-1 , 0.428 g·g-1 and 0.0716 g/g, respectively. The square error of cell growth models, glucose consumption model and human-like collagen formation were almost all around 94%, which indicated that the kinetic model could describe the actual change well. According to the target, that is, to gain the highest productivity of human-like collagen, the feeding rate (F) was worked out on the basis of Pontryagin's minimum principle. In the verification experiments, the specific growth rate was controlled at 0.15 and 0.04 h-1 at the fed-batch and induction phase, respectively. The result showed that the concentrations of cell and human-like collagen could reach 87.6 and 6.11 g·L-1, and they were raised by 17.9 and 18.6%, respectively.
Key words: Fed-batch culture, human-like collagen, maximum specific growth rate, Pontryagin's minimum principle, recombinant Escherichia coli.
, Glucose concentration, g·L-1; P, human-like protein density, g·L-1;SF, flux glucose concentration, g·L-1; t, time, h; t0, the starting time, h; tf, the final time, h; J, the goal function; λ(t), Covariant vector; H, Hamilton function; Y*x/s,apparent yield, overall stoichiometric cell yield coefficient (grams of cell substrate consumed per gram of cell), g·g-1; Yp/s, product yield coefficient, g·g-1; μ, specific growth rate, h-1; μmax, the maximum specific growth rate, h-1; σ, specific rate of substrate disappearance, h-1; π, specific rate of product formation, h-1; α, yield coefficient of collagen accumulation rate associated with cell growth rate, g·g-1; β,variable macrokinetic parameter, yield coefficient of collagen accumulation rate associated with cell growth rate, g·g-1·h-1.
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