Creation of a mirror-image artificial protein synthesis system

Date: 14th March 2019

The majority of amino acids can exist in two isomeric forms; mirror images described as L- and D-forms – depending on how they rotate light – and which cannot be superimposed onto each other.  In nature, however, only L-forms of amino acids are manufactured within the cell and subsequently incorporated into proteins. In essence at the amino acid level, nature is left-handed and an entire alternate proteome exists through the incorporation of D-form amino acids into proteins.

Now a group at the DKFZ in Germany & The Scripps Institute have started to create the basic elements of a synthetic D-form protein synthesis system by generating a ligase from D-amino acids that has the ability to connect the ends of mirror-image DNA strands together (those in the L-form conformation) whilst having no reported activity on naturally-occurring D-DNA or other naturally-occurring cofactors.

Is this the beginning of a synthetic mirror-image cell system? Just maybe, the groups’ ultimate aim is to create a mirror-image structure equivalent to a ribosome which would allow many D-form proteins to be produced; a cellular D-protein factory as such.

What benefit would come from this? Well, it’s a small leap to imagine applications where D-form proteins confer differential binding properties; specificities; bioproduction properties; or immunogenicity effects. Indeed, could this breakthrough towards a mirror-image proteome, open-up an entirely new proteome of new possibilities…

Weidmann, J., M. Schnölzer, P. E. Dawson and J. D. Hoheisel. (2019) “Copying Life: Synthesis of an Enzymatically Active Mirror-Image DNA-Ligase Made of D-Amino Acids.” Cell Chemical Biology.