Recoding a Bacterial Genome Allows Biosynthesis of Proteins with New Functions

This GRO exhibited improved properties for incorporation of nonstandard amino acids that expand the chemical diversity of proteins in vivo.

The Science

Engineered bacteria are used in biotechnology for producing enzymes and other proteins as well as the biological molecules they synthesize. However, the spectrum of possible proteins that can be biotechnologically produced is limited by the 20 amino acids in the genetic code. One way to expand the possibilities of potential engineered protein functions is to add more amino acids to the repertoire that can be incorporated into proteins. In a recent article published in Science, researchers at Yale and Harvard Universities altered the genome of the model bacterium Escherichia coli so that one of the three stop codons (three-letter words that constitute the genetic code) is no longer used. In this recoded E. coli strain, the freed stop codon (UAG) could now be used to incorporate new amino acids by providing the necessary machinery (a modified tRNA that recognizes UAG and a special aminoacyl–tRNA synthetase, the enzyme that loads amino acids onto the tRNA). With these tools, the researchers showed that they can incorporate novel amino acids into a selected protein without affecting the rest of the bacterial proteins, while maintaining a normal cellular physiology. In addition, the recoded cells are less susceptible to viral infection, and the risk of transferring altered DNA to other organisms is minimized because the normal protein synthesis machinery will not work properly with the recoded genes from the recoded strain. This work has tremendous implications for engineering new organisms that can be used for producing novel proteins that perform new functions needed in DOE-relevant processes such as biofuels production.

BER Program Manager

Pablo Rabinowicz

U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]


Lajoie, M. J., A. J. Rovner, D. B. Goodman, H.-R. Aerni, A. D. Haimovich, G. Kuznetsov, J. A. Mercer, H. H. Wang, P. A. Carr, J. A. Mosberg, N. Rohland, P. G. Schultz, J. M. Jacobson, J. Rinehart, G. M. Church, and F. J. Isaacs. 2013. “Genomically Recoded Organisms Expand Biological Functions,” Science 342, 357-60. DOI:10.1126/science.1241459.