Sprecher
Beschreibung
Precise control of biomolecular interactions is central to synthetic biology, therapeutics, and biosensing [1,2]. Enzyme-inhibitor complexes, in particular, represent a powerful but underutilized axis for programmable regulation due to their inherent reversibility and specificity [3]. However, conventional approaches to modulate these systems often lack dynamic tunability and contextual responsiveness [4]. Here, we present a modular platform that harnesses the programmability of synthetic nucleic acids and the versatility of gene networks to dynamically regulate enzyme-inhibitor complexes. Specifically, synthetic gene circuits are engineered to respond to specific targets by transcribing functional RNA strands in a highly programmable and orthogonal manner. These RNA strands act as regulatory elements that modulate enzyme-inhibitor interactions. By encoding these logic-driven responses in transcriptional modules, we achieve repression or activation of enzymatic activity. We demonstrate this concept using different enzyme-inhibitor systems and validate how transcriptionally encoded RNA regulators can be used to achieve input-specific and dose-responsive control in a tunable and reversible way. This platform offers a new route to dynamic biochemical control, with broad implications for therapeutic enzyme regulation, biosensing and synthetic biology.
References
1) Silverman AD, Gollakota DV, & Jewett MC (2020). Cell-free gene expression: an expanded repertoire of applications. Nature Reviews Genetics, 21, 151-170. https://doi.org/10.1038/s41576-019-0186-3
2) Jung JK, Alam KK, Verosloff MS, Capdevila DA, Desmau M, Clauer PR, Lee JW, Nguyen PQ, Pastén PA, Matiasek SJ, Gaillard JF, Giedroc DP, Collins JJ, & Lucks JB (2022). Cell-free biosensors for rapid detection of water contaminants. Nature Biotechnology, 40, 682-692. https://doi.org/10.1038/s41587-022-01208-7
3) Pandi A, Vasquez JJ, Ferrante T, Balasubramanian S, & Del Vecchio D (2023). Design of dynamic enzyme regulation using modular transcriptional inhibitors. Nature Communications, 14, 1853. https://doi.org/10.1038/s41467-023-37341-1
4) Xu H, Beisel CL, & Lu TK (2021). Synthetic biology strategies for programmable enzyme control. Trends in Biotechnology, 39, 472-485. https://doi.org/10.1016/j.tibtech.2020.10.012
