Influence of Bioreactor Hydraulic Characteristics on a Saccharomyces Cerevisiae Fed-batch Culture: Hydrodynamic Modelling and Scale-down Investigations

Overview

Journal J Ind Microbiol Biotechnol

Publisher Oxford University Press

Specialty Biotechnology

Date 2009 Apr 8

PMID 19350298

Citations 1

Authors

Annick Lejeune

F Delvigne

P Thonart

Affiliations

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Abstract

Yeast is a widely used microorganism at the industrial level because of its biomass and metabolite production capabilities. However, due to its sensitivity to the glucose effect, problems occur during scale-up to the industrial scale. Hydrodynamic conditions are not ideal in large-scale bioreactors, and glucose concentration gradients can arise when these bioreactors are operating in fed-batch mode. We have studied the effects of such gradients in a scale-down reactor, which consists of a mixed part linked to a non-mixed part by a recirculation pump, in order to mimic the hydrodynamic conditions encountered at the large scale. During the fermentation tests in the scale-down reactor, there was a drop in both biomass yield (ratio between the biomass produced and the glucose added) and trehalose production and an increase in both fermentation time (time between inoculation and beginning of stationary phase) and ethanol production. We have developed a stochastic model which explains these effects as the result of an induction process determined mainly by the hydrodynamic conditions. The concentration profiles experienced by the microorganisms during the scale-down tests were expressed and linked to the biomass yields of the scale-down tests.

Citing Articles

The effect of growth rate on the production and vitality of non-Saccharomyces wine yeast in aerobic fed-batch culture.

Barkhuizen J, Coetzee G, van Rensburg E, Gorgens J Bioprocess Biosyst Eng. 2021; 44(12):2655-2665.

PMID: 34499236 DOI: 10.1007/s00449-021-02634-3.

References

Sweere A, Mesters J, Janse L, Luyben K, Kossen N . Experimental simulation of oxygen profiles and their influence on baker's yeast production: I. One-fermentor system. Biotechnol Bioeng. 1988; 31(6):567-78. DOI: 10.1002/bit.260310609. View

Hewitt C, Onyeaka H, Lewis G, Taylor I, Nienow A . A comparison of high cell density fed-batch fermentations involving both induced and non-induced recombinant Escherichia coli under well-mixed small-scale and simulated poorly mixed large-scale conditions. Biotechnol Bioeng. 2006; 96(3):495-505. DOI: 10.1002/bit.21127. View

Neubauer P, Haggstrom L, Enfors S . Influence of substrate oscillations on acetate formation and growth yield in Escherichia coli glucose limited fed-batch cultivations. Biotechnol Bioeng. 1995; 47(2):139-46. DOI: 10.1002/bit.260470204. View

Lara A, Leal L, Flores N, Gosset G, Bolivar F, Ramirez O . Transcriptional and metabolic response of recombinant Escherichia coli to spatial dissolved oxygen tension gradients simulated in a scale-down system. Biotechnol Bioeng. 2005; 93(2):372-85. DOI: 10.1002/bit.20704. View

Sandoval-Basurto E, Gosset G, Bolivar F, Ramirez O . Culture of Escherichia coli under dissolved oxygen gradients simulated in a two-compartment scale-down system: metabolic response and production of recombinant protein. Biotechnol Bioeng. 2004; 89(4):453-63. DOI: 10.1002/bit.20383. View

Reijenga K, Bakker B, van der Weijden C, Westerhoff H . Training of yeast cell dynamics. FEBS J. 2005; 272(7):1616-24. DOI: 10.1111/j.1742-4658.2005.04582.x. View

Lin H, Neubauer P . Influence of controlled glucose oscillations on a fed-batch process of recombinant Escherichia coli. J Biotechnol. 2000; 79(1):27-37. DOI: 10.1016/s0168-1656(00)00217-0. View

Sweere A, Janse L, Luyben K, Kossen N . Experimental simulation of oxygen profiles and their influence on baker's yeast production: II. Two-fermentor system. Biotechnol Bioeng. 1988; 31(6):579-86. DOI: 10.1002/bit.260310610. View

Li F, Hashimura Y, Pendleton R, Harms J, Collins E, Lee B . A systematic approach for scale-down model development and characterization of commercial cell culture processes. Biotechnol Prog. 2006; 22(3):696-703. DOI: 10.1021/bp0504041. View

10.

Delvigne F, Lejeune A, Destain J, Thonart P . Stochastic models to study the impact of mixing on a fed-batch culture of Saccharomyces cerevisiae. Biotechnol Prog. 2006; 22(1):259-69. DOI: 10.1021/bp050255m. View

11.

Bylund F, Castan A, Mikkola R, Veide A, Larsson G . Influence of scale-up on the quality of recombinant human growth hormone. Biotechnol Bioeng. 2000; 69(2):119-28. DOI: 10.1002/(sici)1097-0290(20000720)69:2<119::aid-bit1>3.0.co;2-9. View

12.

Papagianni M, Mattey M, Kristiansen B . Design of a tubular loop bioreactor for scale-up and scale-down of fermentation processes. Biotechnol Prog. 2003; 19(5):1498-504. DOI: 10.1021/bp030002y. View

13.

Onyeaka H, Nienow A, Hewitt C . Further studies related to the scale-up of high cell density Escherichia coli fed-batch fermentations: the additional effect of a changing microenvironment when using aqueous ammonia to control pH. Biotechnol Bioeng. 2003; 84(4):474-84. DOI: 10.1002/bit.10805. View

14.

Serrato J, Palomares L, Meneses-Acosta A, Ramirez O . Heterogeneous conditions in dissolved oxygen affect N-glycosylation but not productivity of a monoclonal antibody in hybridoma cultures. Biotechnol Bioeng. 2004; 88(2):176-88. DOI: 10.1002/bit.20232. View

15.

Postma E, Verduyn C, Scheffers W, van Dijken J . Enzymic analysis of the crabtree effect in glucose-limited chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microbiol. 1989; 55(2):468-77. PMC: 184133. DOI: 10.1128/aem.55.2.468-477.1989. View

16.

Namdev P, Thompson B, Gray M . Effect of feed zone in fed-batch fermentations of Saccharomyces cerevisiae. Biotechnol Bioeng. 1992; 40(2):235-46. DOI: 10.1002/bit.260400207. View

17.

Enfors S, Jahic M, Rozkov A, Xu B, Hecker M, Jurgen B . Physiological responses to mixing in large scale bioreactors. J Biotechnol. 2001; 85(2):175-85. DOI: 10.1016/s0168-1656(00)00365-5. View

18.

Ronkart S, Paquot M, Fougnies C, Deroanne C, Van Herck J, Blecker C . Determination of total water content in inulin using the volumetric Karl Fischer titration. Talanta. 2008; 70(5):1006-10. DOI: 10.1016/j.talanta.2006.02.024. View

19.

Lara A, Vazquez-Limon C, Gosset G, Bolivar F, Lopez-Munguia A, Ramirez O . Engineering Escherichia coli to improve culture performance and reduce formation of by-products during recombinant protein production under transient intermittent anaerobic conditions. Biotechnol Bioeng. 2006; 94(6):1164-75. DOI: 10.1002/bit.20954. View

20.

Fowler J, Dunlop E . Effects of reactant heterogeneity and mixing on catabolite repression in cultures of Saccharomyces cerevisiae. Biotechnol Bioeng. 1989; 33(8):1039-46. DOI: 10.1002/bit.260330813. View