Optimal Temperature Control Policy for a Two‐Stage Recombinant Fermentation Process

Hortaçsu, Amable; Ryu, Dewey D. Y.

doi:10.1021/bp00006a001

Cited by 19 publications

(13 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that during prolonged periods of derepression of the λpL/pR promoters at temperatures up to 42°C, the propagation of plasmid-free cells is favored [16,126,127]. Furthermore, the fraction of plasmid-free cells under derepression at 38 or 40°C has been reported to be lower than at 41°C or above [16,127].…”

Section: Phenomena and Variables That Modulate The Productivity In Thmentioning

confidence: 99%

See 1 more Smart Citation

Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters

Valdez‐Cruz

Caspeta

Pérez³

et al. 2010

Microb Cell Fact

146

108

View full text Add to dashboard Cite

The temperature inducible expression system, based on the pL and/or pR phage lambda promoters regulated by the thermolabile cI857 repressor has been widely use to produce recombinant proteins in prokariotic cells. In this expression system, induction of heterologous protein is achieved by increasing the culture temperature, generally above 37°C. Concomitant to the overexpression of heterologous protein, the increase in temperature also causes a variety of complex stress responses. Many studies have reported the use of such temperature inducible expression system, however only few discuss the simultaneous stress effects caused by recombinant protein production and the up-shift in temperature. Understanding the integral effect of such responses should be useful to develop improved strategies for high yield protein production and recovery. Here, we describe the current status of the heat inducible expression system based on the pL and/or pR λ phage promoters, focusing on recent developments on expression vehicles, the stress responses at the molecular and physiological level that occur after heat induction, and bioprocessing factors that affect protein overexpression, including culture operation variables and induction strategies.

show abstract

Section: Phenomena and Variables That Modulate The Productivity In Thmentioning

confidence: 99%

“…Furthermore, the fraction of plasmid-free cells under derepression at 38 or 40°C has been reported to be lower than at 41°C or above [16,127]. For example, Sayadi et al [128] detected that 12 and 48% of the cells had lost the plasmid after 250 generations at 37 and 42°C, respectively.…”

Section: Phenomena and Variables That Modulate The Productivity In Thmentioning

confidence: 99%

Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters

Valdez‐Cruz

Caspeta

Pérez³

et al. 2010

Microb Cell Fact

146

108

View full text Add to dashboard Cite

show abstract

“…1988) products. Recombinant plasmid stability and other parameters of the cultures have been independently analyzed in these conditions (Siegel and Dewey, 1985;Hortacsu and Ryu, 1990). In a previous work (Cubarsi et al.…”

Section: Introductionmentioning

confidence: 99%

Conditions for a continuous production of transient microbial products in a two-stage fermentation system

Cubarsi

Villaverde

1993

Biotechnol Lett

View full text Add to dashboard Cite

The optimal residence time in the inducing reactor of a continuous two-stage system has been studied in order to maximize the yield in such a process. The attention has been focused on the case in which the product (or one of its forms) appears in the culture only transiently after the induction. Whereas in some cases the two-stage system is able to improve the yield and to allow a continuous product concentration in the outgoing stream, in others, and depending on how the product is accumulated in the induced culture, no optimal residence time can be found, and a higher productivity will be achieved by using the one-stage continuous strategy or a batch fermentation.

show abstract

“…The optimal temperature control policy for the two-stage system was considered in a previous study. 3 The dilution rate determines the apparent or averaged growth rate of a heterogeneous population of plasmid-harboring and plasmid-free cells. The growth rate, in turn, affects the plasmid content of the cells, the stability of the plasmid-harboring cells, and the cellular metabolic rates for the translation and transcription steps necessary for gene expression.…”

Section: Introductionmentioning

confidence: 99%

Optimization of a two‐stage recombinant fermentation process: The dilution rate effect

Hortaçsu

Ryu

1991

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

The effects of dilution rates on the performance of a two-stage fermentation system for a recombinant Escherichia coli culture were studied. Dilution rate determines the apparent or averaged specific growth rate of a heterogeneous population of cells in the recombinant culture. The specific growth rate affects the genetic parameters involved in product formation in the second stage, such as plasmid stability, plasmid content, and specific gene expression rate. Kinetic models and correlations were developed for these parameters based on experimental data. Simulations of plasmid stability in the first stage showed that for longer fermentation periods, plasmid stability is better at higher dilution rates. However, the plasmid content is lower at these dilution rates. The optimal apparent specific growth rate for maximum productivity in the second stage was determined using two methods: (1) direct search for a constant specific growth rate, and (2) dynamic optimization using the maximum principle for a time-dependent specific growth rate profile. The results of the calculations showed that the optimum constant apparent specific growth rate for maximum over-all productivity is 0.40 h(-1). This coincides with the optimal specific growth rate for maximum plasmid content in the expressed stage. A 3.5% increase in overall productivity can be obtained by using a linear time dependent apparent specific growth rate control, micro(2)(t) = 0.0007t, in the course of the fermentation time.

show abstract

Optimal Temperature Control Policy for a Two‐Stage Recombinant Fermentation Process

Cited by 19 publications

References 7 publications

Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters

Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters

Conditions for a continuous production of transient microbial products in a two-stage fermentation system

Optimization of a two‐stage recombinant fermentation process: The dilution rate effect

Contact Info

Product

Resources

About