PMID- 22714954 OWN - NLM STAT- MEDLINE DCOM- 20130723 LR - 20211021 IS - 1476-5535 (Electronic) IS - 1367-5435 (Linking) VI - 39 IP - 10 DP - 2012 Oct TI - Optimization of fermentation parameters in phage production using response surface methodology. PG - 1515-22 AB - Previously, we used computer-controlled fermentation technology to improve the yield of filamentous phage produced in Escherichia coli by 10-fold (Grieco et al., Bioprocess Biosyst Eng 32:773-779, 2009). In the current study, three major fermentation parameters (temperature, dissolved oxygen [DO], and pH) were investigated using design of experiments (DOE) methodology. Response surface methodology (RSM) was employed to create a process model and determine the optimal conditions for maximal phage production. The experimental data fitted best to a quadratic model (p < 0.0001). Temperature and pH, but not DO, proved to be significant variables. The model predicted a theoretical optimal condition for maximal bacteriophage production at temperature of 28.1 degrees C and pH 6.9. A validation run resulted in phage production [3.49 x 10(11) transducing units (TU)/mL] comparable to the predicted value (2.86 x 10(11) TU/mL). This represented a 7-fold increase in phage production above that obtained without optimization, resulting in a 70-fold increase above that achieved by shake flask culture alone. FAU - Grieco, Sung-Hye H AU - Grieco SH AD - Centre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. sunghye.grieco@ubc.ca FAU - Wong, Ann Y K AU - Wong AY FAU - Dunbar, W Scott AU - Dunbar WS FAU - MacGillivray, Ross T A AU - MacGillivray RT FAU - Curtis, Susan B AU - Curtis SB LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120620 PL - Germany TA - J Ind Microbiol Biotechnol JT - Journal of industrial microbiology & biotechnology JID - 9705544 RN - S88TT14065 (Oxygen) SB - IM MH - Analysis of Variance MH - Escherichia coli/metabolism/*virology MH - *Fermentation MH - Hydrogen-Ion Concentration MH - Inovirus/*growth & development MH - Models, Biological MH - Oxygen/metabolism MH - Reproducibility of Results MH - Temperature EDAT- 2012/06/21 06:00 MHDA- 2013/07/24 06:00 CRDT- 2012/06/21 06:00 PHST- 2012/01/24 00:00 [received] PHST- 2012/05/04 00:00 [accepted] PHST- 2012/06/21 06:00 [entrez] PHST- 2012/06/21 06:00 [pubmed] PHST- 2013/07/24 06:00 [medline] AID - 10.1007/s10295-012-1148-3 [doi] PST - ppublish SO - J Ind Microbiol Biotechnol. 2012 Oct;39(10):1515-22. doi: 10.1007/s10295-012-1148-3. Epub 2012 Jun 20.