Biological systems use G protein-coupled receptors (GPCRs), tyrosine receptor kinases, gated ion channels, and nuclear receptors to detect chemicals in their environment. GPCRs are particularly interesting as they bind the most diverse array of chemicals, from neurotransmitters and hormones, to odorants and flavors. Of the ~ 800 GPCRs, 360 are non-sensory with ~130 of them targeted by FDA approved drugs. The remainder are called sensory GPCRs, and are involved in olfaction (400), taste (33) and light detection (10). Over the last eight years, we have used our yeast-based GPCR sensor system to detect advanced biofuel precursors (Mukherjee et al. 2015), microbially produced chemicals (Ehrenworth et al. 2017; Sarria et al. 2018), odorants (Yasi et al. 2019), and for drug discovery applications (Yasi et al. 2019). We are now using GPCRs to enable synthetic cells to sense their environment and engineering the GPCRs themselves to gain insight into how they activate different downstream pathways.
- Olfactory receptor-based sensors for biomedical applications
- GPCR-based sensors for the detection of commodity chemicals
As chemists, we are interested in leveraging biological systems to produce chemicals from renewables. In particular, our focus is on chemicals that biological systems have a comparative advantage in producing at large scale due to their chemical structure or constrains imposed on the production process. Over the last eight years, we have developed platforms for the production of the jet fuel precursor pinene (Sarria et al. 2014), advanced biodiesel precursors, medium-chain fatty acids (Sarria et al. 2018), the pharmaceutical tetrahydrobiopterin (Ehrenworth et al. 2015; Kiattisewee et al. 2021) and the pharmaceutical intermediate hydroxystrictosidine (Ehrenworth et al. 2015), and the commodity chemical adipic acid (Kruyer et al. 2020). Currently, we are engineering systems for the bioproduction of advanced biofuels on Mars and pharmaceutical intermediates in cell-free systems.
- In situ production of rocket fuel in Mars
- Membrane-based cell-free systems for chemical bioproduction
Synthetic cells can be generated by encapsulating cell-free systems into liposomes. The membrane of synthetic cells can thus be tailored by changing the liposome composition. We are developing membrane augmented cell free systems to facilitate the functional heterologous expression of membrane proteins for bioindustrial applications (Kruyer et al. 2021) .
- Engineering synthetic cells that respond to their environment