Incorporation of non-canonical amino acids (ncAAs) into protein tends to be less efficient compared to proteinogenic amino acids (Paas) since tRNA charged with ncAA has weaker affinity to EF-Tu, the sole translation factor responsible for recruiting tRNA charged with Paas to the ribosome. We are tackling this problem by aiming to engineer a new elongation factor that is responsible for tRNAs charged with ncAAs using directed evolution approaches.

In addition, the Ellington lab engages in multitude of projects involving the engineering translational components for improved ncAA incorporation both in vivo and in vitro (Figure A). We seek to introduce new-to-nature functions in proteins through the incorporation of ncAAs. In particular, we focused on tunable orthogonal reversible covalent (TORC) bonding interaction (Figure B). TORC chemistry allows complexation and dissociation of small molecules or biomacromolecule at a covalent level and controlled by changes in physical stimuli, such as pH. We’re currently focusing on engineering aminoacyl tRNA synthetase (aaRS) and tRNA pair to incorporate unnatural amino acids containing these TORC moieties into protein. Ultimately, we want to demonstrate the application of this chemistry in modulating protein-protein interaction and supramolecular assembly.

Associated Lab Members :

Satoshi Ishida

Phuoc Ngo