Designed to be scaled up

Research studies for the design and construction of new protein and chemical production strains are often performed as typical proof of concept studies to demonstrate the principal feasibility of  microbial production of a chemical compound or a protein at high product titers. However, thus generated strains frequently suffer from lower performance in long cultivation processes and higher volume.

Employing Pichia pastorisas a host strain we put special emphasis on vector design, the development of new chassis strains and alternative biosynthetic pathway assembly strategies in order to obtain robust microbial strains with stable maintenance of multiple gene copies, opportunities for stepwise increase of transcript levels in bioreactor cultivations and enhanced reliability in larger volumes.

Enzymes and model pathways were used to illustrate the differences in classical and new generation strain design. The applied methodology is generic and can be transfered to other hosts, as demonstrated by examples using E. coli, S. cerevisiaeand CHO.

Acknowledgements: The research leading to these results has received funding from the Innovative Medicines Initiative Joint Undertaking project CHEM21 under grant agreement n°115360, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.