Background: Recombinant protein production is a process of great industrial interest, with products that range\nfrom pharmaceuticals to biofuels. Since high level production of recombinant protein imposes significant stress in\nthe host organism, several methods have been developed over the years to optimize protein production. So far,\nthese trial-and-error techniques have proved laborious and sensitive to process parameters, while there has been\nno attempt to address the problem by applying Synthetic Biology principles and methods, such as integration of\nstandardized parts in novel synthetic circuits.\nResults: We present a novel self-regulatory protein production system that couples the control of recombinant\nprotein production with a stress-induced, negative feedback mechanism. The synthetic circuit allows the downregulation\nof recombinant protein expression through a stress-induced promoter. We used E. coli as the host\norganism, since it is widely used in recombinant processes. Our results show that the introduction of the selfregulatory\ncircuit increases the soluble/insoluble ratio of recombinant protein at the expense of total protein yield.\nTo further elucidate the dynamics of the system, we developed a computational model that is in agreement with\nthe observed experimental data, and provides insight on the interplay between protein solubility and yield.\nConclusion: Our work introduces the idea of a self-regulatory circuit for recombinant protein products, and paves\nthe way for processes with reduced external control or monitoring needs. It demonstrates that the library of\nstandard biological parts serves as a valuable resource for initial synthetic blocks that needs to be further refined to\nbe successfully applied in practical problems of biotechnological significance. Finally, the development of a\npredictive model in conjunction with experimental validation facilitates a better understanding of the underlying\ndynamics and can be used as a guide to experimental design.
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