Proteins are the workhorses of our existence.   These "helmsmen of the cell" are composed of amino acids, whose sequence is already defined by the heritable information in every living being and transport substances, convey messages and carry out vital processes in their role as molecular machines. 

The translation of this information during the production of proteins (protein synthesis) is determined by the genetic code and 20 amino acids form the standard set of which proteins are built.

In natural conditions, several hundred amino acids can be found and  new amino acids can also be produced in the laboratory which differ from the 20 standard amino acids because by their integration in proteins, scientists can systematically change specific structural and biological characteristics of proteins - but only one type of synthetic amino acid could be inserted into a protein during a single experiment in a residue-specific manner; thus, only one property of a protein could be modified at once.

Now scientists at the Max Planck Institute of Biochemistry (MPIB) in Martinsried near Munich, Germany, have succeeded, for the first time, in integrating three different synthetic amino acids into one protein in a single experiment.

three synthetic amino acids in one protein
For the first time, three amino acids of one protein could be changed at the same time in a single experiment.  Image: Nediljko Budisa / MPI of Biochemistry

Nediljko Budisa, head of the research group Molecular Biotechnology at the MPIB, says the ability to substitute three different natural amino acids with synthetic ones at the same time in a single experiment is a big advance.   "The research area of genetic code engineering and code extension has with this result reached a new development phase." 

Budisa’s method could be of great importance because the production of artificial proteins by genetic code engineering in his view demonstrates a solid basis for the development of new technologies.

"During integration, synthetic amino acids confer their characteristics to proteins. Thus, the development will allow the synthesis of totally new classes of products, whose chemical synthesis has not been possible so far by conventional protein engineering using only the 20 standard amino acids," says Budisa. "Thanks to our method, in the future it will be possible to tailor industrial relevant proteins with novel properties: for example proteins containing medical components."

Citation: S. Lepthien, L. Merkel, N. Budisa, 'In vivo double and triple labeling of proteins using synthetic amino acids', Angewandte Chemie, June 24, 2010 DOI 10.1002/anie.201000439