Biosensors – Design & engineering
Living organisms have evolved a plethora of sensing systems for the intra- and extracellular detection of small molecules, ions, and physical parameters. We exploit and incorporate these sensory mechanisms in synthetic circuits to devise genetically-encoded biosensors, which are highly valuable for a wide range of biotechnological applications. Ligand-binding properties of sensory proteins can further be modified by protein engineering, yielding custom-made biosensors for detecting different compounds of interest.
Genetically-encoded biosensors allow for the rapid high-throughput screening of vast libraries of genetically diverse microorganisms at the single-cell level. When combined with fluorescence-activated cell sorting (FACS), biosensors enable the analysis of >104 variants per second. The powerful FACS approach renders costly individual cultivation and evaluation of all clones in a given library unnecessary, and thus significantly speeds up design–build–test cycles. In particular, transcription factor-based biosensors are successfully designed and used for strain engineering at IBG1.
Biosensor-driven adaptive evolution
In engineering disciplines, the possibility of process improvement via adaptive laboratory evolution (ALE) is a feature unique to biotechnology. Biosensor-based synthetic evolution strategies enable selection for increased small molecule production by linking metabolic productivity to growth as a selectable trait. Advances in next-generation sequencing and automation technologies will foster the application of ALE strategies to streamline microbial strains for bioproduction and enhance our understanding of biological systems.