Engineering Life’s Language: Streamlined Approaches to Efficient Genetic Code Expansion

The genetic code is the foundation for all life. With few exceptions, the translation of nucleic acid messages into proteins follows conserved rules, which are defined by codons that specify each of the 20 proteinogenic amino acids. Supplementing translation with non-canonical amino acids (ncAAs) can yield protein sequences with new-to-nature functions, but existing ncAA incorporation strategies suffer from low efficiency and context dependence. Recently, our lab has developed technologies rooted in bioengineering and directed evolution that overcome longstanding limitations in genetic code expansion. In this presentation, I will discuss our efforts to develop new-to-nature proteins and peptides by altering the cell’s translation apparatus, including tRNAs, mRNAs, and the ribosome itself. Given the generality of our approaches and streamlined resources, our findings will accelerate innovations in multiplexed genetic code expansion and enable the discovery of chemically diverse biomolecules for researcher-defined applications.

Speaker: Ahmed Badran, Scripps