Abstract
Biological processes are subject to the influence of numerous factors and their interactions, which may be non-linear in nature. In a recombinant protein production experiment, understanding the relative importance of these factors, and their influence on the yield and quality of the recombinant protein being produced, is an essential part of its optimisation. In many cases, implementing a design of experiments (DoE) approach has delivered this understanding. This chapter aims to provide the reader with useful pointers in applying a DoE strategy to improve the yields of recombinant yeast cultures.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Anthony J (2003) Design of experiments for engineers and scientists. Butterworth-Heinemann, Oxford
Holmes WJ, Darby RAJ, Wilks MDB, Smith R, Bill RM (2009) Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime. Microb Cell Fact 8:35
Czitrom V (1999) One-factor-at-a-time versus designed experiments. Amer Statistician 53:2
Fisher RA (1971) The design of experiments, 9th edn. Macmillan, London
Rao RS, Kumar CG, Prakasham RS, Hobbs PJ (2008) The Taguchi methodology as a statistical tool for biotechnological applications: a critical appraisal. Biotechnol J 3:510–523
Knospel F, Schindler RK, Lubberstedt M, Petzolt S, Gerlach JC, Zeilinger K (2010) Optimization of a serum-free culture medium for mouse embryonic stem cells using design of experiments (DoE) methodology. Cytotechnology 62:557–571
Bisgaard S, Fuller HT (1994–1995) Analysis of factorial experiments with defects or defectives as a response. Quality Eng 7:429–443
Yuan L-L, Li Y-Q, Wang Y, Zhang X-H, Xu Y-Q (2008) Optimization of critical medium components using response surface methodology for phenazine-1-carboxylic acid production by Pseudomonas sp. M-18Q. J Biosci Bioeng 105:232–237
de Aguiar PF, Bourguignon B, Khots MS, Massart DL, Phan-Than-Luu R (1995) D-optimal designs. Chemometrics Internat Lab Sys 30:199–210
Luo W, Pla-Roca M, Juncker D (2011) Taguchi design-based optimization of sandwich immunoassay microarrays for detecting breast cancer biomarkers. Anal Chem 83:5767–5774
Myers RH, Montgomery DC (1995) Response surface methodology: process and product optimization using designed experiments, 1st edn. Wiley, New York
Einsfeldt K, Severo Junior JB, Correa Argondizzo AP, Medeiros MA, Alves TL, Almeida RV, Larentis AL (2011) Cloning and expression of protease ClpP from Streptococcus pneumoniae in Escherichia coli: Study of the influence of kanamycin and IPTG concentration on cell growth, recombinant protein production and plasmid stability. Vaccine. doi:10.1016/j.vaccine.2011.05.073
Ferreira SL, Bruns RE, Ferreira HS, Matos GD, David JM, Brandao GC, da Silva EG, Portugal LA, dos Reis PS, Souza AS, dos Santos WN (2007) Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta 597:179–186
Montgomery DC, Peck EA (1982) Introduction to linear regression analysis. Wiley, New York
Mandenius CF, Brundin A (2008) Bioprocess optimization using design-of-experiments methodology. Biotechnol Prog 24:1191–1203
Shi F, Xu Z, Cen P (2006) Efficient production of poly-gamma-glutamic acid by Bacillus subtilis ZJU-7. Appl Biochem Biotechnol 133:271–282
Garcia-Arrazola R, Dawson P, Buchanan I, Doyle B, Fearn T, Titchener-Hooker N, Baganz F (2005) Evaluation of the effects and interactions of mixing and oxygen transfer on the production of Fab’ antibody fragments in Escherichia coli fermentation with gas blending. Bioprocess Biosyst Eng 27:365–374
Wang Y-H, Yang B, Ren J, Dong M-L, Liang D, Xu AL (2005) Optimization of medium composition for the production of clavulanic acid by Streptomyces clavuligerus. Process Biochem 40:1161–1166
Pritchett J, Baldwin SA (2004) The effect of nitrogen source on yield and glycosylation of a human cystatin C mutant expressed in Pichia pastoris. J Ind Microbiol Biotechnol 31:553–558
Adinarayana K, Ellaiah P, Srinivasulu B, Bhavani Devi R, Adinarayana G (2003) Response surface methodological approach to optimize the nutritional parameters for neomycin production by Streptomyces marinensis under solid-state fermentation. Process Biochem 38:1565–1572
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+business Media, LLC
About this protocol
Cite this protocol
Bora, N., Bawa, Z., Bill, R.M., Wilks, M.D.B. (2012). The Implementation of a Design of Experiments Strategy to Increase Recombinant Protein Yields in Yeast (Review). In: Bill, R. (eds) Recombinant Protein Production in Yeast. Methods in Molecular Biology, vol 866. Humana Press. https://doi.org/10.1007/978-1-61779-770-5_11
Download citation
DOI: https://doi.org/10.1007/978-1-61779-770-5_11
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-769-9
Online ISBN: 978-1-61779-770-5
eBook Packages: Springer Protocols