Artificially expanded genetic alphabet evolves enzymes for the first time

An artificially expanded DNA alphabet has been shown to evolve simple enzymes for the first time. The work, which added two synthetic nucleotide building blocks to the usual four of DNA to build a library of molecules, demonstrates how such libraries could offer enhanced chemical diversity over standard DNA for finding biomedically relevant molecules, as well as offer clues to how life began.

DNA usually only comprises four nucleotides – A, C, T and G – so the richness of possible sequences to build molecular libraries is limited, particularly with shorter oligonucleotide sequences, or oligos. One solution is to add functional groups to natural nucleotides to create novel molecules. But an alternative approach that has emerged over the past two decades is to expand the genetic alphabet beyond four bases using synthetic nucleotides.