MRC Laboratory of Molecular Biology, Cambridge

A molecular biologist gets excited about making designer proteins in cells.

The genetic code describes the relationship between the heritable information in the genome and the amino acids that are strung together to make proteins. This code, like any that contains redundancy, is open to hacking, and I have long been fascinated by how the process of translation, by which cells string amino acids together, might be reprogrammed to make new polymers. Several labs have already manipulated cells to incorporate designer amino acids into their proteins.

But Peter Schultz and his colleagues at the Scripps Research Institute in La Jolla, California, have achieved something remarkable. Proteins are made from a set of 20 amino acids, each of which contains an amine and a carboxylic acid group flanking a central carbon atom. Schultz's team engineered a bacterial cell to work with amino-acid-like molecules called -hydroxy acids that have an alcohol group where the amine would normally be. During translation, instead of forming an amide bond to link polymer subunits, this -hydroxy acid forms an ester bond (J. Guo et al. Angew. Chem. 120, 734–737; 2008).

Replacing a nitrogen and a hydrogen atom in a polymer chain with an oxygen atom might seem like a slight change, but it means that a protein can now be specifically cut at the ester bond in basic solution. Making esters from -hydroxy acids may first have been achieved with ribosomes in a test tube in the 1970s, but turning the process into a heritable, genetic property is a major advance: it takes synthetic biologists closer to creating organisms with designer codes to make new polymers.

One day soon, the creativity and skill with which chemists can make molecules will be coupled to the selective power of organismal evolution. And we will watch new life forms boot up.