Regulated multicistronic expression technology for mammalian metabolic engineering

Contemporary basic research is rapidly revealing increasingly complex molec ular regulatory networks which are often interconnected via key signal inte grators. These connections among regulatory and catalytic networks often fr ustrate bioengineers as promising metabolic engineering strategies are bypa ssed by compensatory metabolic responses or cause unexpected, undesired out comes such as apoptosis, product protein degradation or inappropriate post- translational modification. Therefore, for metabolic engineering to achieve greater success in mammalian cell culture processes and to become importan t for future applications such as gene therapy and tissue engineering, this technology must be enhanced to allow simultaneous, in cases conditional, r eshaping of metabolic pathways to access difficult-to-attain cell states. R ecent advances in this new territory of multigene metabolic engineering are intimately linked to the development of multicistronic expression technolo gy which allows the simultaneous, and in some cases, regulated expression o f several genes in mammalian cells. Here we review recent achievements in m ulticistronic expression technology in view of multigene metabolic engineer ing.