Influence of bioreactor hydraulic characteristics on a Saccharomyces cerevisiae fed-batch culture: hydrodynamic modelling and scale-down investigations.
Lejeune, Annick; Delvigne, Frank; Thonart, Philippe
2010 • In Journal of Industrial Microbiology and Biotechnology, 37, p. 225-236
[en] 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.
Delvigne, Frank ; Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech
Thonart, Philippe ; Université de Liège - ULiège > Gembloux Agro-Bio Tech > Gembloux Agro-Bio Tech - Biochimie et microbiologie industrielles
Language :
English
Title :
Influence of bioreactor hydraulic characteristics on a Saccharomyces cerevisiae fed-batch culture: hydrodynamic modelling and scale-down investigations.
Publication date :
2010
Journal title :
Journal of Industrial Microbiology and Biotechnology
Gaspar A (1999) Etude des interactions entre les paramètres biologiques et les grandeurs physiques liées à l'agitation et à l'aération lors de la production de xylanases par Penicillium canescens. In: Unité de Bio-Industries 1999. Faculté universitaire des Sciences agronomiques de Gembloux: Gembloux
SO Enfors M Jahic A Rozkov B Xu M Hecker B Jürgen E Krüger T Schweder G Hamer D O'Beirne, et al. 2001 Physiological responses to mixing in large scale bioreactors J Biotechnol 85 2 175 185 10.1016/S0168-1656(00)00365-5 10.1016/S0168-1656(00)00365-5 1:CAS:528:DC%2BD3MXpsVGrsw%3D%3D 11165362 (Pubitemid 32124719)
F Guillard C Tragardh 1999 Modeling of the performance of industrial bioreactors with a dynamic microenvironment approach: a critical review Chem Eng J 22 3 187 195 1:CAS:528:DyaK1MXitlChs7Y%3D
APJ Sweere L Janse KCAM Luyben NWF Kossen 1988 Experimental simulation of oxygen profiles and their influence on baker's yeast production: I. One-fermentor system Biotechnol Bioeng 31 567 578 10.1002/bit.260310609 10.1002/bit.260310609 1:CAS:528:DyaL1cXit1Sgsb4%3D 18584647 (Pubitemid 18594978)
Jem JK (1989) Scale-down techniques for fermentation. Biopharmacy 3:30-39
S George G Larson K Olsson SO Enfors 1998 Comparison of the baker's yeast performance in laboratory and production scale Bioprocess Biosyst Eng 18 135 142 10.1007/PL00008979 1:CAS:528:DyaK1cXhtVWis78%3D
F Li Y Hashimura R Pendleton J Harms E Collins B Lee 2006 A systematic approach for scale-down model development and characterization of commercial cell culture processes Biotechnol Prog 22 696 703 10.1021/bp0504041 10.1021/bp0504041 16739951 (Pubitemid 43877437)
APJ Sweere KCAM Luyben NWF Kossen 1987 Regime analysis and scale-down: tools to investigate the performance of bioreactors Enz Microb Technol 9 386 398 10.1016/0141-0229(87)90133-5 10.1016/0141-0229(87)90133-5 1:CAS:528: DyaL2sXltFCitLY%3D (Pubitemid 17617017)
PK Namdev BG Thompson MR Gray 1992 Effect of feed zone in fed-batch fermentations of Saccharomyces cerevisiae Biotechnol Bioeng 40 235 246 10.1002/bit.260400207 10.1002/bit.260400207 1:CAS:528:DyaK38XksVKlu74%3D 18601109
P Neubauer L Haggstrom SO Enfors 1995 Influence in substrate oscillations on acetate formation and growth yield in E coli glucose limited fed-batch cultivations Biotechnol Bioeng 47 139 146 10.1002/bit.260470204 10.1002/bit.260470204 1:CAS:528:DyaK2MXmtl2gs7Y%3D 18623386
APJ Sweere L Janse KCAM Luyben 1988 Experimental simulation of oxygen profiles and their influence on baker's yeast production: II. Two-fermentor system Biotechnol Bioeng 31 579 586 10.1002/bit.260310610 10.1002/bit.260310610 1:CAS:528:DyaL1cXit1Sgsb8%3D 18584648 (Pubitemid 18594979)
NMG Oosterhuis NM Groesbeek APC Olivier NWF Kossen 1983 Scale-down aspects of the gluconic acid fermentations Biotechnol Lett 5 3 141 146 10.1007/BF00131892 10.1007/BF00131892 1:CAS:528:DyaL3sXhslOnuro%3D
JD Fowler EH Dunlop 1989 Effects of reactant heterogeneity and mixing on catabolite repression in culture of Saccharomyces cerevisiae Biotechnol Bioeng 33 1039 1046 10.1002/bit.260330813 10.1002/bit.260330813 1:CAS:528: DyaL1MXhsFakt7k%3D 18588018
G Cortes MA Trujillo-Roldan OT Ramirez E Galindo 2005 Production of β-galactosidase by Kluyveromyces marxianus under oscillating dissolved oxygen tension Process Biochem 40 773 778 10.1016/j.procbio.2004.02.001 10.1016/j.procbio.2004.02.001 1:CAS:528:DC%2BD2cXpt1Wgtrw%3D (Pubitemid 39437881)
JA Serrato LA Palomares A Meneses-Acosta OT Ramirez 2004 Heterogeneous conditions in dissolved oxygen affect N-glycosylation but not productivity of a monoclonal antibody in hybridoma cultures Biotechnol Bioeng 88 2 176 188 10.1002/bit.20232 10.1002/bit.20232 1:CAS:528:DC%2BD2cXot1Kisr8%3D 15449295 (Pubitemid 39422989)
H Onyeaka AW Nienow CJ Hewitt 2003 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 84 4 474 484 10.1002/bit.10805 10.1002/bit.10805 1:CAS:528:DC%2BD3sXos1Gmtb4%3D 14574706 (Pubitemid 37280219)
M Papagianni M Mattey B Kristiansen 2003 Design of a tubular loop bioreactor for scale-up and scale-down of fermentation processes Biotechnol Prog 19 1498 1504 10.1021/bp030002y 10.1021/bp030002y 1:CAS:528:DC%2BD3sXlvVGks74%3D 14524711 (Pubitemid 37250040)
HY Lin P Neubauer 2000 Influence of controlled glucose oscillations on a fed-batch process of recombinant Escherichia coli J Biotechnol 79 27 37 10.1016/S0168-1656(00)00217-0 10.1016/S0168-1656(00)00217-0 1:CAS:528: DC%2BD3cXjsFygurw%3D 10817339 (Pubitemid 30160714)
F Bylund A Castan R Mikkola A Veide G Larsson 2000 Influence of scale-up on the quality of recombinant human growth hormone Biotechnol Bioeng 69 2 119 128 10.1002/(SICI)1097-0290(20000720)69:2<119::AID-BIT1>3.0.CO;2-9 10.1002/(SICI)1097-0290(20000720)69:2<119::AID-BIT1>3.0.CO;2-9 1:CAS:528:DC%2BD3cXkt1agsrY%3D 10861391 (Pubitemid 30430083)
AR Lara C Vazquez-Limon G Gosset F Bolivar A Lopez-Munguia OT Ramirez 2006 Engineering Escherichia coli to improve culture performance and reduce formation of by-products during recombinant protein production under transient intermittent anaerobic conditions Biotechnol Bioeng 94 6 1164 1175 10.1002/bit.20954 10.1002/bit.20954 1:CAS:528:DC%2BD28XnvF2ksrc%3D 16718678 (Pubitemid 44221062)
AR Lara L Leal N Flores G Gosset F Bolivar OT Ramirez 2006 Transcriptional and metabolic response of recombinant Escherichia coli to spatial dissolved oxygen tension gradients simulated in a scale-down system Biotechnol Bioeng 93 2 372 385 10.1002/bit.20704 10.1002/bit.20704 1:CAS:528:DC%2BD28Xht1Oit7o%3D 16187334
EA Sandoval-Basurto G Gosset F Bolivar OT Ramirez 2005 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 89 4 453 463 10.1002/bit.20383 10.1002/bit.20383 1:CAS:528:DC%2BD2MXhtFektLc%3D 15609273 (Pubitemid 40288906)
CJ Hewitt H Onyeaka G Lewis IW Taylor AW Nienow 2007 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 96 3 495 505 10.1002/bit.21127 10.1002/bit.21127 1:CAS:528:DC%2BD2sXhtVajtLo%3D 16902956 (Pubitemid 46232355)
F Delvigne J Destain P Thonart 2005 Structured mixing model for stirred bioreactor: an extension to a stochastic approach Chem Eng J 113 1 1 12 10.1016/j.cej.2005.06.007 10.1016/j.cej.2005.06.007 1:CAS:528:DC%2BD2MXhtVyrsb3O (Pubitemid 41398151)
P Vrabel RGJM van der Lans FN Van Der Schot KCAM Luyben B Xu SO Enfors 2001 CMA: Integration of fluid dynamics and microbial kinetics in modelling of large-scale fermentations Chem Eng J 84 463 474 10.1016/S1385-8947(00)00271-0 10.1016/S1385-8947(00)00271-0 1:CAS:528:DC%2BD3MXptVSrsbk%3D (Pubitemid 34057328)
J Zahradnik R Mann M Fiavola D Vlaev SD Vlaev V Lossev P Seichter 2001 A network-of-zones analysis of mixing and mass transfer in three industrial bioreactors Chem Eng Sci 56 485 492 10.1016/S0009-2509(00)00252-9 10.1016/S0009-2509(00)00252-9 1:CAS:528:DC%2BD3MXht1yktb4%3D (Pubitemid 32376120)
D Vlaev R Mann V Lossev SD Vlaev J Zahradnik 2000 Macro-mixing and Streptomyces fradiae: modelling oxygen and nutrient segregation in an industrial bioreactor Trans. IchemE 78 354 362 10.1205/026387600527473 10.1205/026387600527473 1:CAS:528:DC%2BD3cXktF2ms7g%3D (Pubitemid 30354939)
YQ Cui RGJM van der Lans J Noorman KCAM Luyben 1996 Compartment mixing model for stirred reactors with multiple impellers Trans IchemE Part A 74 261 271 1:CAS:528:DyaK28XivFKitr8%3D
P Vrabel RGJM van der Lans KCAM Luyben L Boon AN Nienow 2000 Mixing in large-scale vessels stirred with multiple radial or radial and axial up-pumping impellers: modeling and measurements Chem Eng Sci 55 5881 5896 10.1016/S0009-2509(00)00175-5 10.1016/S0009-2509(00)00175-5 1:CAS:528: DC%2BD3cXot1OisLk%3D
R Mann SK Pillai AM El-Hamouz P Ying A Togatorop RB Edwards 1995 Computational fluid mixing for stirred vessels: progress from seeing to believing Chem Eng Sci 59 39 50 1:CAS:528:DyaK2MXnslyisbc%3D
R Mann D Vlaev V Lossev SD Vlaev J Zahradnik P Seichter 1997 A network-of-zones analysis of the fundamentals of gas-liquid mixing in an industrial stirred bioreactor Récent Progrès Génie Procédés 11 223 230 1:CAS:528:DyaK2sXks1Gmtrc%3D
H Berthiaux 2000 Analysis of grinding process by Markov chain Chem Eng Sci 55 4117 4127 10.1016/S0009-2509(00)00086-5 10.1016/S0009-2509(00)00086-5 1:CAS:528:DC%2BD3cXks12gtLo%3D (Pubitemid 30620942)
F Delvigne A Lejeune J Destain P Thonart 2006 Stochastic models to study the impact of mixing on a fed-batch culture of Saccharomyces cerevisiae Biotechnol Prog 22 259 269 10.1021/bp050255m 10.1021/bp050255m 1:CAS:528:DC%2BD2MXhtFymsLzL 16454518 (Pubitemid 43224234)
Walker GM (1998) Yeast physiology and biotechnology. Wiley, London
SN Ronkart M Paquot C Fougnies C Deroanne J-C Van Herck C Bleker 2006 Determination of total water content in inulin using the volumetric Karl Fischer titration Talanta 70 1006 1010 10.1016/j.talanta.2006.02.024 10.1016/j.talanta.2006.02.024 1:CAS:528:DC%2BD28XhtFyqur%2FL 18970874 (Pubitemid 44767852)
SN Ronkart C Blecker C Fougnies JC Van Herck J Wouters M Paquot 2006 Determination of physical changes of inulin related to sorption isotherms: an X-ray diffraction, modulated differential scanning calorimetry and environmental scanning electron microscopy study Carbohydr Polym 63 210 217 10.1016/j.carbpol.2005.08.030 10.1016/j.carbpol.2005.08.030 1:CAS:528: DC%2BD28XptVSlsw%3D%3D (Pubitemid 43144664)
B Mayr P Horvat A Moser 1992 Engineering approach to mixing quantification in bioreactors Bioprocess Biosyst Eng 8 137 143 10.1007/BF01254229 1:CAS:528:DyaK3sXkt1Krsrs%3D
E Postma C Verduyn WA Scheffers JP van Dijken 1989 Enzymic analysis of the Crabtree effect in glucose-limited chemostat cultures of Saccharomyces cerevisiae Appl Environ Microbiol 55 2 468 477 1:CAS:528:DyaL1MXhtFWmsLs%3D 2566299
A Fiechter W Seghezzi 1992 Regulation of glucose metabolism in growing yeast cells J Biotechnol 27 27 45 10.1016/0168-1656(92)90028-8 10.1016/0168-1656(92)90028-8 1:CAS:528:DyaK3sXht1Sms74%3D (Pubitemid 23016017)
Lejeune A(2005) Dimensionnement et extrapolation d'un procédé fed-batch de production de la levure Saccharomyces cerevisiae (boulardii) par modélisation structurée des paramètres du génie chimique. Faculté Universitaire des Sciences Agronomiques, Gembloux
KA Reijenga BM Bakker CC van der Weijden HV Westerhoff 2005 Training of yeast cell dynamics FEBS J 272 1616 1624 10.1111/j.1742-4658.2005.04582.x 10.1111/j.1742-4658.2005.04582.x 1:CAS:528:DC%2BD2MXjtlShtb8%3D 15794749 (Pubitemid 40516212)
F Delvigne A Lejeune J Destain P Thonart 2006 Modelling of the substrate heterogeneities experienced by a limited microbial population in scale-down and in large-scale bioreactors Chem Eng J 120 157 167 10.1016/j.cej.2006.03.034 10.1016/j.cej.2006.03.034 1:CAS:528:DC%2BD28XlvFKjsr4%3D (Pubitemid 43903670)