Recoding Genomes to Expand Life’s Functional Repertoire

The conservation of the genetic code permits organisms to share beneficial traits via horizontal gene transfer, and enables the accurate expression of heterologous genes in non-native organisms. Fundamental changes to the genetic code could significantly enhance our understanding of the origins of the canonical code and reveal new subtleties of how genetic information is encoded and exchanged. I will describe the construction of Genomically Recoded Organisms (GROs), in which all 321 UAG stop codons were replaced with the synonymous UAA stop codon in E. coli. This GRO exhibited improved properties for incorporation of nonstandard amino acids that expand the chemical diversity of proteins in vivo and demonstrated multi-virus resistance. Finally, I will describe the engineering of the GRO to depend on synthetic amino acids aimed at construction of safe GMOs unable to grow in the wild. This works demonstrates the application of genome-scale engineering toward the fundamental redesign of genomes and construction of orthogonal biological systems with new properties.