A synthetic molecular system capable of mirror-image genetic replication and transcription.
The overwhelmingly homochiral nature of life has left a puzzle as to whether mirror-image biological systems based on a chirally inverted version of molecular machinery could also have existed. Here we report that two key steps in the central dogma of molecular biology, the template-directed polymerization of DNA and transcription into RNA, can be catalysed by a chemically synthesized D-amino acid polymerase on an L-DNA template. We also show that two chirally mirrored versions of the 174-residue African swine fever virus polymerase X could operate in a racemic mixture without significant enantiomeric cross-inhibition to the activity of each other. Furthermore, we demonstrate that a functionally active L-DNAzyme could be enzymatically produced using the D-amino acid polymerase. The establishment of such molecular systems with an opposite handedness highlights the potential to exploit enzymatically produced mirror-image biomolecules as research and therapeutic tools.
School of Life Sciences, Center for Synthetic and Systems Biology, Ministry of Education Key Laboratory of Bioinformatics, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
Zimou
Z
Wang
Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
Weiliang
W
Xu
Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
Lei
L
Liu
School of Life Sciences, Center for Synthetic and Systems Biology, Ministry of Education Key Laboratory of Bioinformatics, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing 100084, China.
Ting F
TF
Zhu
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D009690:Nucleic Acid Conformation; D058105:Polymerization; D012313:RNA / Q000737:chemistry; D013237:Stereoisomerism; D014158:Transcription, Genetic / Q000235:genetics
D000596:Amino Acids; D012313:RNA; D004247:DNA