A new code for life

One of the apparent certitudes in the life sciences is the universality of the genetic code: four nucleotides specify 64 triplet codons to encode the 20 amino acids from which all organisms synthesize proteins. But this certainty is no longer guaranteed. Several research groups have succeeded in expanding the genetic code of both prokaryotic and eukaryotic organisms by adding non‐natural amino acids. This may lead to the synthesis of proteins with novel biological, chemical and physical properties with significant consequences for biotechnology and medicine.> …the ability to modify proteins specifically with custom‐made amino acids holds tremendous potential for both basic and applied researchThe expansion of the genetic code—not to be confused with standard genetic engineering of proteins with naturally occurring amino acids—started about 15 years ago, when research groups led by Richard Chamberlin at the University of California (Irvine, USA) and Peter Schultz at the Scripps Research Institute (La Jolla, CA, USA) developed the ‘amber suppression method’ for incorporating non‐natural amino acids into proteins (Fig 1). This method uses chemically aminoacylated amber suppressor tRNAs to introduce non‐natural amino acids into large proteins in vitro and in microinjected cells. Since then, biologists have expanded their molecular toolbox with new strategies, such as the aminoacylation of tRNAs with non‐natural amino acids based on the action of either ribozymes or appropriately mutated aminoacyl‐tRNA synthetases, or by generating non‐standard codons that contain four or five bases or include non‐natural base pairs (Hohsaka & Sisido, 2002; Wang & Shultz, 2002). These methods now make it feasible to encode artificial amino acids genetically and to insert them into proteins in vivo with high selectivity and fidelity. First applied to Escherichia coli (Wang et al , 2001), a modified in vivo protocol for the yeast Saccharomyces cerevisiae (Chin et al , 2003) has now introduced the possibility …