School of Biotechnology
Div. of Bioprocess Technology, KTH
SE-106 91 Stockholm, Sweden
Telephone: +46-(0)8-5537 8316
Telefax: +46-(0)8-5537 8323
E-mail: Gen.Larsson@biotech.kth.se
Visiting address: Roslagstullsbacken 21, 1st floor

RESEARCH AREAS

• Scale up and scale down of bioprocesses

Studies of microenvironment formation in bioreactors of various sizes and during production processes. Coupling of microenvironment formation to process parameters specifically turbulence. Studies of effects on microbial performance under shifting environmental conditions (scale down reactors) such as feast and famine. Comparison of large scale and scale down performance. 
Model organisms: yeast, E.coli and P. chrysogenum.

• Expression of recombinant proteins in E.coli

The work is based on several issues of recombinant protein production, both of physiological and physical character such as: new promoters, fedbatch feed profile optimisation, inducer titration, proteolysis ans inclusion body formation as well as the E.coli membrane structure and function during protein expression. The latter work includes both phospholipid and fatty acid studies but also accumulation of proteins. We work with several model proteins of which one has been expression of antibody fragments in the periplasm.

• Cell engineering of E.coli

We are working on a set of engineered cells which we call "fedbatch simulators". These are designed to work at different growth rates although they are grown under batch conditions. These cells are further not producing acetic acid which makes them a very good choice in early process development since the simulation of fedbatch conditions can be very early evalated and transition to the indsutrial scale might thus be facilitated.

• Surface expression of proteins in E.coli

We are using a specific mechanism for the expressions of proteins to the surface and to the medium in E.coli, the autotransporter system. This system is presently optimised for production of particularly difficult proteins but also for expression of covalently linked enzymes on the surface. The latter system is used for a combined production and immobilisation of the biocatalyst aimed for production of chiral building blocks for the pharmaceutical industry. 

Recent publications:

• Boström M, Larsson G (2005) Process design for recombinant protein production based on the promoter P_malK, Appl Microbiol Biotechnol 66:200-208

• Sandén AM, Boström M, Markland K, Larsson G (2005) Solubility and proteolysis of the MalE and MalE31 proteins during overproduction in Escherichia coli, Biotechnol Bioeng 90:240-247

• Shokri A, Larsson G (2004) Characterisation of the Escherichia coli membrane during fed-batch cultivation, Microbial Cell Factories 3:9

• Boström M, Markland K, Sandén AM, Hedhammar M, Hober S, Larsson G (2004) Effect of substrate feed rate on protein secretion, degradation and inclusion body formation in Escherichia coli, Appl Microbiol Biotechnol 68:82-90

• Shokri A, Veide A, Larsson G (2006) RelA1 gene control of Escherichia coli lipid structure and cell performance during glucose-limited fedbatch cultivations 73:464-473

• Backlund E, Markland K, Larsson G (2008) Cell engineering of Escherichia coli allows high cell density accumulation without fed-batch process control, Bioproc Biosys Eng 31:11-20

• Bäcklund E, Reeks D, Markland K, Weir N, Bowering L, Larsson G (2008) Fed-batch design for maximizing periplasmic antibody fragment product retention, J Biotech 135:358-365