Exometabolome analysis reveals hypoxia at the up-scaling of a Saccharomyces cerevisiae high-cell density fed-batch biopharmaceutical process

Microbial Cell Factories

Volumn 13, Issue 1, 2014, Pages

  Fu, Zhibiao ^a   Verderame, Thomas D ^a   Leighton, Julie M ^a   Sampey, Brante P ^b   Appelbaum, Edward R ^a   Patel, Pramatesh S ^a   Aon, Juan C ^a  

^a GLAXOSMITHKLINE   (United States)

^b METABOLON INC   (United States)

Author keywords

Exometabolomics; Fermentation process; Hypoxia; Mass transfer coefficient; Metabolome profiling; Oxygen uptake rate; Saccharomyces cerevisiae; Scale up

Indexed keywords

CARBON; DILUENT; DISSOLVED OXYGEN; ERGOSTEROL; MEVALONIC ACID; OXYGEN;

ARTICLE; CARBON METABOLISM; CATABOLISM; CONTROLLED STUDY; FED BATCH FERMENTATION; FERMENTATION OPTIMIZATION; FUNGAL BIOMASS; FUNGAL METABOLISM; HYPOXIA; INDUSTRIAL PRODUCTION; METABOLIC STRESS; METABOLOMICS; NONHUMAN; PRESSURE; SACCHAROMYCES CEREVISIAE; SCALE UP;

SACCHAROMYCES CEREVISIAE;

ANAEROBIOSIS; BATCH CELL CULTURE TECHNIQUES; BIOMASS; CITRIC ACID CYCLE; ERGOSTEROL; GLYCOLYSIS; HYDROGEN-ION CONCENTRATION; METABOLOME; METABOLOMICS; MEVALONIC ACID; OXYGEN; SACCHAROMYCES CEREVISIAE; TEMPERATURE;

EID: 84899489010     PISSN: None     EISSN: 14752859     Source Type: Journal    
DOI: 10.1186/1475-2859-13-32     Document Type: Article

References (35)

1. Ferrer-Miralles N, Domingo-Espin J, Corchero JL, Vazquez E, Villaverde A. Microbial factories for recombinant pharmaceuticals. Microb Cell Fact 2009, 8:17-24. 10.1186/1475-2859-8-17, 2669800, 19317892.
2. Holmes WJ, Darby RAJ, Wilks MDB, Smith R, Bill RM. Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime. Microb Cell Fact 2009, 8:35-48. 10.1186/1475-2859-8-35, 2717918, 19570229.
3. Siurkus J, Panula-Perala J, Horn U, Kraft M, Rimseliene R, Neubauer P. Novel approach of high cell density recombinant bioprocess development: optimization and scale-up from microlitre to pilot scales while maintaining the fed-batch cultivation mode of E. coli cultures. Microb Cell Fact 2010, 9:35-51. 10.1186/1475-2859-9-35, 2890543, 20487563.
4. Amanullah A, BuckLand BC, Nienow AW. Mixing in the fermentation and cell culture industries. Handbook of Industrial Mixing: Science and Practice 2003, 1071-1170. New York: John Wiley & Sons, Paul EL, Atiemo-Obeng VA, Kresta SM.
5. Xu B, Jahic M, Blomsten G, Enfors SO. Glucose overflow metabolism and mixed-acid fermentation in aerobic large-scale fed-batch processes with Escherichia coli. Appl Microbiol Biotechnol 1999, 51:564-571. 10.1007/s002530051433, 10390814.
6. Vrabel P, van der Lans RGJM, Luyben KCAM, Boon LA, Nienow AW. Mixing in large-scale vessels, stirred with multiple radial and axial pumping up impellers: modeling and measurements. Chem Eng Sci 2000, 55:5881-5896.
7. Enfors SO, Jahic M, Rozkov A, Xu B, Hecker M, Jurgen B, Kruger E, Shweder T, Hamer G, O'Beirne D, Noisommit-Rizzi N, Reuss M, Boone L, Hewitt C, McFarlane C, Nienow A, Kovacs T, Trägårdh C, Fuchs L, Revstedt J, Friberg PC, Hjertager B, Blomsten G, Skogman H, Hjort S, Hoeks F, Lin HY, Neubauer P, van der Lans R, Luyben K, Vrabel P, Manelius A. Physiological responses to mixing in large bioreactors. J Biotechnol 2001, 85:175-185. 10.1016/S0168-1656(00)00365-5, 11165362.
8. Bylund F, Collet E, Enfors SO, Larsson G. Substrate gradient formation in the large-scale bioreactor lowers cell yield and increases by-product formation. Bioproc Eng 1998, 18:171-180.
9. Oosterhuis NMG, Kossen NWF, Olivier APC, Schenk ES. Scale-down and optimization studies of the gluconic acid fermentation by Gluconobacter oxydans. Biotechnol Bioeng 1985, 27:711-720. 10.1002/bit.260270521, 18553727.
10. Amanullah A, Christensen LH, Hansen K, Nienow AW, Thomas CR. Dependence of morphology on agitation intensity in fed-batch cultures of Aspergillus oryzae and its implications for recombinant protein production. Biotechnol Bioeng 2002, 77:815-826. 10.1002/bit.10181, 11835142.
11. Riley GL, Tucker KG, Paul GC, Thomas CR. Effect of biomass concentration and mycelial morphology on fermentation broth rheology. Biotechnol Bioeng 2000, 68:160-172. 10.1002/(SICI)1097-0290(20000420)68:2<160::AID-BIT5>3.0.CO;2-P, 10712732.
12. Junker BH. Scale-up methodologies for Escherichia coli and yeast fermentation processes. J Biosci Bioeng 2004, 97:347-364. 10.1016/S1389-1723(04)70218-2, 16233642.
13. Hewitt CJ, Nebe-Von Caron G, Axelsson B, McFarlane CM, Nienow AW. Studies related to the scale-up of high-cell-density E. coli fed-batch fermentations using multiparameter flow cytometry: effect of changing microenvironment with respect to glucose and dissolved oxygen concentration. Biotechnol Bioeng 2000, 70:381-390. 10.1002/1097-0290(20001120)70:4<381::AID-BIT3>3.0.CO;2-0, 11005920.
14. Nienow AW. Hydrodynamics of stirred bioreactors. App Mech Rev 1998, 51:3-32.
15. Schweder T, Krüger E, Xu B, Jürgen B, Blomsten G, Enfors SO, Hecker M. Monitoring of genes that respond to process-related stress in large-scale bioprocesses. Biotechnol Bioeng 1999, 65:151-159. 10.1002/(SICI)1097-0290(19991020)65:2<151::AID-BIT4>3.0.CO;2-V, 10458735.
16. Paczia N, Nilgen A, Lehmann T, Gatgens J, Wiechert W, Noack S. Extensive exometabolome analysis reveals extended overflow metabolism in various microorganism. Microb Cell Fact 2012, 11:122-136. 10.1186/1475-2859-11-122, 3526501, 22963408.
17. Fu Z, Leighton J, Cheng A, Appelbaum E, Aon JC. Optimization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate Bayesian approach. Biotechnol Prog 2012, 28:1095-1105. 10.1002/btpr.1557, 22581591.
18. Epstein CB, Waddle JA, Hale W, Dave V, Thornton J, Macatee TL, Garner HR, Butow RA. Genome-wide responses to mitochondrial dysfunction. Mol Biol Cell 2001, 12:297-308. 10.1091/mbc.12.2.297, 30944, 11179416.
19. Valerio A, D'Antona G, Nisoli E. Branched-chain amino acids, mitochondrial biogenesis, and healthspan: an evolucionary perspective. Aging 2011, 3:464-478. 3156598, 21566257.
20. Linton JD. The relationship between metabolite production and the growth efficiency of the producing organism. FEMS Microbiol Rev 1990, 75:1-18.
21. Enfors SO. Preface. Advances in Biochemical Engineering/Biotechnology-Physiological Stress Responses in Bioprocesses 2004, 89. New York: Springer, Enfors SO.
22. Soini J, Ukkonen K, Neubauer P. High cell density media for Escherichia coli are generally designed for aerobic cultivations - consequences for large-scale bioprocesses and shake flask cultures. Microb Cell Fact 2008, 7:26-36. 10.1186/1475-2859-7-26, 2526063, 18687130.
23. Wick LM, Egli T. Molecular components of physiological stress responses in E. coli. Advances in Biochemical Engineering/Biotechnology-Physiological Stress Responses in Bioprocesses 2004, New York: Springer, Enfors SO, 89: 1-46.
24. Malinowski JJ, Lafforgue L, Goma G. Rheological behavior of high density continuous cultures of Saccharomyces cerevisiae. J Ferment Technol 1987, 65:319-323.
25. Bhargava S, Wenger KS, Marten MR. Pulsed feeding during fed-batch Aspergillus oryzae fermentation leads to improved oxygen mass transfer. Biotechnol Prog 2003, 19:1091-1094. 10.1021/bp025694p, 12790687.
26. Tuffile CM, Pinho F. Determination of oxygen transfer coefficients in viscous streptomycete fermentations. Biotechnol Bioeng 1970, 12:849-871.
27. Nienow AW. Aeration-Biotechnology. Kirk Othmer Encyclopedia of Chemical Technology 2003, New York: John Wiley & Sons, Nienow AW, 1: 730-747.
28. Rintala E, Toivari M, Pitkanen JP, Wiebe M, Ruohonen L, Penttila M. Low oxygen levels as a trigger for enhancement of respiratory metabolism in Saccharomyces cerevisiae. BMC Genomics 2009, 10:461-480. 10.1186/1471-2164-10-461, 2767370, 19804647.
29. Abe F, Hiraki T. Mechanistic role of ergosterol in membrane rigidity and cycloheximide resistance in Saccharomyces cerevisiae. Biochim Biophys Acta 2009, 1788:743-752. 10.1016/j.bbamem.2008.12.002, 19118519.
30. Bagnat M, Keranen S, Shevchenko A, Simons K. Lipids rafts function in biosynthetic delivery of proteins to the cell surface in yeast. Proc Natl Acad Sci U S A 2000, 97:3254-3259. 10.1073/pnas.97.7.3254, 16225, 10716729.
31. Baumann K, Adelantado N, Lang C, Mattanovich D, Ferrer P. Protein trafficking, ergosterol biosynthesis and membrane physics impact recombinant protein secretion in Pichia pastoris. Microbiol Cell Fact 2011, 10:93-108.
32. Linton JD, Rye AJ. The relationship between energetic efficiency in different microorganisms and the rate and type of metabolite over-produced. J Ind Microbiol 1989, 4:85-96.
33. Ukkonen K, Veijola J, Vasal A, Neubauer P. Effect of culture medium, host strain and oxygen transfer on recombinant Fab antibody fragment yield and leakage to medium in shaken E. coli cultures. Microb Cell Fact 2013, 12:73-86. 10.1186/1475-2859-12-73, 3733871, 23895637.
34. Goodey AR, Sleep D, van Urk H, Berezenko S, Woodrow JR, Johnson RA, Wood PC, Burton SJ, Quirk AV, Coghlan DJ, Wilson MJ. High purity albumin and method of producing. 1998, Patent US 5,728,553.
35. Garcia MT, Sanz R, Galceran MT, Puignou L. Use of fluorescent probes for determination of yeast cell viability by gravitational field-flow fractionation. Biotechnol Prog 2006, 22:847-852. 10.1021/bp050421q, 16739970.