A basic biosensor has two modules (see the figure): the sensitive element recognizes and binds analytes, whereas the transducer module transmits and reports signals.
Post-translational biosensors (part a) consist of membrane-bound protein receptors that trigger signal transduction cascades through signalling proteins, such as response regulators of two-component systems. In the example shown, a synthetic protein scaffold was engineered to physically localize the pathway components of the yeast mitogen-activated protein kinase (MAPK) pathway, which here is being triggered by the mating α-factor (Bashor et al., 2008). By recruiting pathway positive and negative modulators (±) to the scaffold, the system can be tuned to enable desired responses to upstream signals (for example, accelerated, delayed or ultrasensitive responses).
The hybrid example (part b) shows a synthetic genetic edge detection circuit (Tabor et al., 2009). The sensitive element is a light–dark sensor, Cph8, made as a chimaera of the photoreceptor domain of the cyanobacteria phytochrome Cph1 and the kinase domain of Escherichia coli EnvZ. This synthetic sensor activates an engineered gene circuit that combines cell–cell communication (genes and promoters of the Lux operon) with a logical AND gate (Plux-λ) to trace the edges of an image. Specifically, the absence of light triggers Cph8 kinase activity, which correspondingly activates the ompC promoter. Cells not receiving light will therefore produce the cell–cell communication molecule 3-oxohexanoyl-homoserine lactone (AHL; yellow circle) through expression of its biosynthetic enzyme LuxI. In addition, these cells will produce the transcriptional repressor CI (grey oval). AHL binds to the constitutively expressed transcription factor LuxR (light blue oval) to activate expression from the Plux-λ promoter, which is simultaneously and dominantly repressed by CI. The result is that only cells that receive light (and therefore do not express the transcriptional repressor CI) and are nearby to AHL-producing dark cells will activate the final gate and produce pigment through β-galactosidase activity (encoded by lacZ).
From: A2, SYNTHETIC BIOLOGY: APPLICATIONS COME OF AGE
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