Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile
Tóm tắt
In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also.
Tài liệu tham khảo
DePalma A (2004) PAT: taking process monitoring to next level. Gen Eng News 24(9):46–47
FDA (2004) Guidance for Industry: PAT—a framework for innovative pharmaceutical manufacturing & quality assurance. http://www.fda.gov/cvm/guidance/published.html
Jenzsch M, Gnoth S, Beck M, Kleinschmidt M, Simutis R, Lübbert A (2006) Open loop control of the biomass concentration within the growth phase of recombinant protein production processes. J Biotechnol (in press)
Jenzsch M, Simutis R, Eisbrenner G, Stückrath I, Lübbert A (2006) Estimation of biomass concentrations in fermentation processes for recombinant protein production. Bioprocess Biosyst Eng 29(1):19–27
Jenzsch M, Simutis R, Lübbert A (2005) Application of model predictive control to cultivation processes for protein production with genetically modified bacteria. In: Pons MN, van Impe JFM (eds) Computer application in biotechnology 2004 (CAB9). IFAC/Elsevier, Amsterdam, pp 511–516, ISBN 0-08-044251-X
Jenzsch M, Simutis R, Lübbert A (2006) Generic model control of the specific growth rate in recombinant Escherichia coli cultivations. J Biotechnol 122(4):483–493
Kim BS, Lee SC, Lee SY, Chang YK, Chang HN (2004) High cell density fed-batch cultivation of Escherichia coli using exponential feeding combined with pH-stat. Bioprocess Biosyst Eng 26:147–150
Lee J, Lee SY, Park S, Middelberg APJ (1999) Control of fed-batch fermentations. Biotechnol Adv 17:29–48
Lee SY (1996) High cell-density culture of Escherichia coli. Trends Biotechnol 14:98–105
Levisauskas D, Galvanauskas V, Henrich S, Wilhelm K, Volk N, Lübbert A (2003) Model-based optimization of viral capsid protein production in fed-batch culture of recombinant Escherichia coli. Bioprocess Biosyst Eng 25:255–262
Levisauskas D, Simutis R, Borvitz D, Lübbert A (1996) Automatic control of the specific growth rate in fed-batch cultivations processes based on exhaust gas analysis. Bioprocess Eng 15(3):145–150
Neidhardt FC, Ingraham JL, Schaechter M (1990) Physiology of the bacterial cell, a molecular approach. Sinauer, Sunderland
Picó-Marco E, Picó J, De Battista H (2005) Sliding mode scheme for adaptive specific growth rate control in biotechnological fed-batch processes. Int J Control 78(2):128–141
Pirt SJ (1975) Principles of microbe and cell cultivation. Blackwell, London, pp 115–117
Riesenberg D, Guthke R (1999) High-cell-density cultivation of microorganisms. Appl Microbiol Biotechnol 51:422–430
Shioya S (1992) Optimization and control in fed-batch bioreactors. Adv Biochem Eng Biotechnol 46:111–142
Soons ZITA, Voogt JA, van Straten G, van Boxtel AJB (2006) Constant specific growth rate in fed-batch cultivation of Bordetella pertussis using adaptive control. J Biotechnol, published online 10-07-2006
Yoon SK, Kang WK, Park TH (1994) Fed-batch operation of recombinant Escherichia coli containing Trp promoter with controlled specific growth rate. Biotechnol Bioeng 43:995–999