Phenotypic instability in microbial cultures severely limits the applicability of synthetic biology. Be it for plastic degradation or vitamin synthesis, persistent gene expression is a must. Therefore, we have created CELLECT, an innovative autoregulatory system that makes
microbial survival dependent on the existence of a target molecule. The system integrates a riboswitch, specific to the target compound, linked to a toxin-antitoxin mechanism that regulates cell survival. The binding of the target molecule to the riboswitch inhibits downstream toxin gene expression, allowing the cell to persist. Conversely, in the absence of the target compound, toxin levels steadily increase, resulting in cell death. CELLECT's versatile design makes it applicable across diverse host organisms for the optimization of microbial production or degradation of any compound. We employed computational models to predict system performance in laboratory experiments and demonstrated its functionality through the continuous bioproduction of vitamin B12 in E. coli.