Copying Life: Synthesis of an Enzymatically Active Mirror-Image DNA-Ligase Made of D-Amino Acids
Related Experiment Video
Updated: Jan 27, 2026

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Joachim Weidmann1, Martina Schnölzer2, Philip E Dawson3
1Functional Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract:
Our objective is the creation of a mirror-image synthetic biology: that is, to mimic, entirely independent of Nature, a biological system and to re-create it from artificial component parts. Utilizing enantiomeric L-nucleotides and D-amino acids rather than the natural components, we use chemical synthesis toward a basic, self-replicating mirror-image biological system. Here, we report the synthesis of a functional DNA-ligase in the D-enantiomeric conformation, which is an exact mirror-image of the natural enzyme, exhibiting DNA ligation activity on chirally inverted nucleic acids in L-conformation, but not acting on natural substrates and with natural co-factors. Starting from the known structure of the Paramecium bursaria chlorella virus 1 DNA-ligase and the homologous but shorter DNA-ligase of Haemophilus influenza, we designed and synthesized chemically peptides, which could then be assembled into a full-length molecule yielding a functional protein. The structure and the activity of the mirror-image ligase were characterized, documenting its enantiospecific functionality.
Related Concept Videos
Amino acids
Amino Acid Catabolism
Amino Acid Biosynthetic Pathways
From DNA to Protein
Recombinant DNA
Genome Copying Errors

