Severely stressed, with their resources depleted, and their cellular machinery working beyond capacity, the host cells that are used for heterologous protein production have no option but to activate their stress response pathways in order to mitigate the accumulating effects of expressing a foreign, possibly toxic, protein at vast quantities. The result is lower protein yield and quality, with many products being misfolded or part of inclusion bodies that need further processing. Recently, new techniques aim to shift the control of protein production from humans to cells and empower the latter to regulate the production process, thus leading to increased protein quality. Herein we provide a perspective on how integrative synthetic biology can be applied to traditional biotechnological applications with potentially transformative results.
Keywords: adaptive control; bioengineering; computational modeling; heterologous protein; recombinant protein production; self-regulation; stress induced response; synthetic biology.