Re-engineering Protein Engineering for Organic Solvents

Many transformative nanotechnologies are engineered proteins—biocatalysts, therapeutics, biosensors, and nanoscale scaffolds. Yet we’ve realized only a fraction of their potential because most natural and engineered proteins only function in water. How can we engineer proteins to work in other important chemical environments (e.g., organic solvents) and replace current industrial processes with biotechnology? These proteins don’t exist in nature, and we lack the tools to build them. I’m re-engineering the protein design ecosystem to make proteins compatible with organic solvents. I use computational design to predict sequences that prefer solubilization in octanol, in vitro transcription/translation to assay protein panels, and NMR to compare solution structures to models. I also develop expression platforms and assays to produce proteins in quantities suitable for structural biology and future industrial applications. Finally, I tackle the challenge of creating directed evolution and screening platforms using FACS-sortable microfluidic double emulsions. With these tools, I aim to engineer new functional proteins and explore regions of sequence space incompatible with water.