Gen Larsson | KTH Royal Institute of Technology (original) (raw)

Papers by Gen Larsson

Microbial cell factories, Jan 28, 2004

BACKGROUND: Important parameters during recombinant protein production in Escherichia coli, such ... more BACKGROUND: Important parameters during recombinant protein production in Escherichia coli, such as productivity and protein activity, are affected by the growth rate. This includes the translocation of protein over the membrane to gain better folding capacity or reduced proteolysis. To vary the growth rate two techniques are available: fedbatch and continuous cultivation, both controlled by the ingoing feed rate. RESULTS: During fedbatch cultivation, E. coli contains phosphatidylethanolamine, phosphatidylglycerol, cardiolipin and saturated fatty acids in amounts which are stable with growth rate. However, the levels of cardiolipin are very high compared to continuous cultivation. The reason for fedbatch triggering of this metabolism is not known but hypothesised to result from an additional need for carbon and energy. The reason could be the dynamic and sometimes rapid changes in growth rate to which the fedbatch cell has at all times to adjust. The membrane flexibility, essential ...

Bioprocess Engineering, 1993

Substrate concentration gradients are likely to appear during large scale fermentations. To study... more Substrate concentration gradients are likely to appear during large scale fermentations. To study effects of such gradients on microorganisms, an aerated scale-down reactor system was constructed. It consists of a plug flow reactor (PFR) and a stirred tank reactor (STR), between which the medium is circulated. The PFR, which is an aerated static mixer reactor, was characterized with respect to

Microbial Cell Factories, 2011

Journal of Biotechnology, 1997

Journal of Biotechnology, 1995

Biotechnology and Bioengineering, 2003

Biotechnology and Bioengineering, 2000

The aerobic fed-batch production of recombinant human growth hormone (rhGH) by Escherichia coli w... more The aerobic fed-batch production of recombinant human growth hormone (rhGH) by Escherichia coli was studied. The goal was to determine the production and protein degradation pattern of this product during fed-batch cultivation and to what extent scale differences depend on the presence of a fed-batch glucose feed zone. Results of laboratory bench-scale, scale-down (SDR), and industrial pilot-scale (3-m(3)) reactor production were compared. In addition to the parameters of product yield and quality, also cell yield, respiration, overflow, mixed acid fermentation, glucose concentration, and cell lysis were studied and compared. The results show that oxygen limitation following glucose overflow was the critical parameter and not the glucose overflow itself. This was verified by the pattern of byproduct formation where formate was the dominating factor and not acetic acid. A correlation between the accumulation of formate, the degree of heterogeneity, and cell lysis was also visualized when recombinant protein was expressed. The production pattern could be mimicked in the SDR reactor for all parameters, except for product quantity and quality, where 30% fewer rhGH-degraded forms were present and where about 80% higher total yield was achieved, resulting in 10% greater accumulation of properly formed rhGH monomer.

Biotechnology and Bioengineering, 2003

Biotechnology and Applied Biochemistry, 2003

Bioprocess Engineering, 1996

Bioprocess Engineering, 1998

Bioprocess Engineering, 1993

A coupled reactor system, consisting of one aerated stirred reactor and one anaerobic plug flow r... more A coupled reactor system, consisting of one aerated stirred reactor and one anaerobic plug flow reactor was constructed. Circulation of microbial cells in this system, is chosen to represent the insufficient mixing conditions, present in a large scale vessel. Hereby it is shown, that oscillating oxygen concentrations, give effects on E.coli metabolism. The hydrogen production, resulting from mixed acid fermentation of anaerobically grown cells, is used to indicate the metabolic changes. These changes are measured as hydrogen concentration in the gas outlet of the aerated fermenter, with a Pd-MOS sensor. The dependency of the hydrogen evolution on the anaerobic residence time is shown, and the relevance of this model system for studies on the bioreactor performance, are discussed.

Bioprocess Engineering, 1988

The effect of oxygen limitation on the respiration rate of Penicillium chrysogenum was studied. T... more The effect of oxygen limitation on the respiration rate of Penicillium chrysogenum was studied. The results show that measurements of critical oxygen tensions within a process that on morphological or on physical grounds exhibits an inhomogenous structure are not likely to resemble the Monod model.