Living Yeast Biosensors Engineered with Synthetic Biology

Sensing is critical across diverse fields ranging from diagnostics for human health, biosecurity, and environmental monitoring. Despite its broad impact there have been few breakthroughs in sensor technology in recent decades. Biological systems are ideal for engineering sensors because they inherently have high sensitivity and specificity. Our laboratory is developing living yeast biosensors built around a modular G-Protein Coupled Receptor (GPCR) and a visual pigment readout. We first demonstrated that the technology could be used to detect fungal pathogens by introducing their respective mating GPCRs in our yeast biosensor strain and detecting their secreted mating peptides. We went on to show that the technology is modular and large numbers of fungal mating peptides and GPCRs could be introduced into the yeast biosensor strains and retain activity and show minimal cross-reactivity. Currently we are adapting the yeast biosensor as a diagnostic for different human health pathogens. We present data that the yeast biosensor can be used to detect Invasive Aspergillosis. In a significant step we move beyond fungal pathogens and demonstrate that directed evolution can be used to engineer a yeast biosensor for SARS-CoV-2. We look forward to the impact of machine learning, integrated devices, and yeast communities on the application of living yeast biosensors to diverse societal challenges.