Synthetic genetic circuits have allowed researchers to rewire cells, opening the door to broad applications in biotechnology, agriculture and medicine. However, these circuits impose a burden on the host cell and compete with endogenous processes for resources. To address these issues, Venturelli et al. recruited the bacterial endoribonuclease MazF, which recognizes an 'ACA' sequence in single-stranded RNA found in over 96% of Escherichia coli transcripts, to divert resources to a protected synthetic genetic circuit by degrading transcripts that contain MazF recognition sites. Recoding the mCherry reporter or glucose dehydrogenase gdh transcripts to lack MazF recognition sites ensures protection from degradation after MazF induction, resulting in enhanced fluorescence or gluconate production, respectively. By building a model of cellular resource allocation, the group revealed the strength of the MazF negative feedback loop and the effectiveness of the stoichiometric inhibitor MazE. Transcriptional profiling of MazF-induced cells uncovered cold-shock regulatory elements that were upregulated in response to MazF activity. Recruiting MazF as a global regulator of transcript stability enabled alteration of resource allocation inside a host cell. The researchers envision that resource allocation control could be used in biotechnological applications by modulating the balance of cell growth and production in a dynamic manner.
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Cloney, R. Playing favorites. Nat Chem Biol 13, 693 (2017). https://doi.org/10.1038/nchembio.2425