African Journal of

  • Abbreviation: Afr. J. Biotechnol.
  • Language: English
  • ISSN: 1684-5315
  • DOI: 10.5897/AJB
  • Start Year: 2002
  • Published Articles: 12209

Full Length Research Paper

Optimizing the feeding operation of recombinant Escherichia coli during fed-batch cultivation based on Pontryagin's minimum principle

Wei Jin1,2, Dai-di Fan1,2*, Yan-e Luo1,2, Lei Chi1,2, Jia-qing Guo1,2, Gao-ping Zhang1,2 and Chen-hui Zhu1,2
1Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi’an 710069, China. 2Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Xi’an 710069, China.
Email: [email protected]

  •  Accepted: 15 June 2011
  •  Published: 19 October 2011


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-1P, human-like protein density, g·L-1;SF, flux glucose concentration, g·L-1t, 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-1Yp/s, product yield coefficient, g·g-1 μ, specific growth rate, h-1 μmax, the maximum specific growth rate, h-1σ, specific rate of substrate disappearance, h-1 π, specific rate of product formation, h-1α, yield coefficient of collagen accumulation rate associated with cell growth rate, g·g-1β,variable macrokinetic parameter, yield coefficient of collagen accumulation rate associated with cell growth rate, g·g-1·h-1.

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