Growth defects and loss-of-function in synthetic gene circuits

摘要: Synthetic gene circuits perturb the physiology of their cellular host. The extra load on endogenous processes shifts equilibrium resource allocation in host, leading to slow growth and reduced biosynthesis. Here we built integrated host-circuit models quantify defects caused by synthetic circuits. Simulations reveal a complex relation between circuit output capacity for expression. For weak induction heterologous genes, protein can be increased at expense defects. Yet stronger induction, reaches tipping point, beyond which both expression rate drop sharply. Extensive simulations across various conditions large regions design space suggest that critical is result ribosomal scarcity. We studied impact transcriptional logic gates, highlights extent burden limit, shape, even break down function. Our approach offers comprehensive framework assess interactions silico, with wide-ranging implications optimization bacterial