Proceedings of the National Academy of Sciences · 2009 · 154 citations · 17 references
Life SciencesBioengineeringBiotechnologyGenetic EngineeringMicrobial BiotechnologySynthetic BiologyAllosteric Protein EngineeringGenetic Circuit DesignGenetic Engineering Of MicroorganismsMicrobial Cell EngineeringMicrobial Synthetic BiologySynthetic Gene CircuitsBand-pass FilteringChemical GradientsDesign PrinciplesEnzyme ActivityEnzyme Activity TuningEnzyme-substrate InteractionsEnzymesEscherichia Coli
Current tuning of synthetic biology relies on re‑engineering components, yet systems that can be tuned by external stimuli are expected to be more versatile. The study aims to engineer E. coli as an externally tunable band‑pass filter for enzyme activity and small molecules, with the goal of extending this strategy to other biological systems. The authors incorporated an enzyme‑substrate attenuator into the genetic network, enabling tunable band‑pass behavior in E.
The current paradigm for tuning synthetic biological systems is through re-engineering system components. Biological systems designed with the inherent ability to be tuned by external stimuli will be more versatile. We engineered Escherichia coli cells to behave as an externally tunable band-pass filter for enzyme activity and small molecules. The band's location can be positioned within a range of 4 orders of magnitude simply by the addition of compounds to the growth medium. Inclusion in the genetic network of an enzyme-substrate pair that functions as an attenuator is a generalizable strategy that enables this tunability. The genetic circuit enabled bacteria growth to be patterned in response to chemical gradients in nonintuitive ways and facilitated the isolation of engineered allosteric enzymes. The application of this strategy to other biological systems will increase their utility for biotechnological applications and their usefulness as a tool for gaining insight into nature's underlying design principles.
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A synthetic multicellular system for programmed pattern formation
Subhayu Basu, Yoram Gerchman, Cynthia H. Collins et al. · Nature · 2005 · 1.2K citations
A fast, robust and tunable synthetic gene oscillator
Jesse Stricker, Scott Cookson, Matthew R. Bennett et al. · Nature · 2008 · 1.2K citations
Life Sciences, Biological Engineering, Molecular Biology +12