Cited by 209Origins and Evolution of LifeRNA and protein synthesis mechanismsDNA and Nucleic Acid Chemistry

A synthetic molecular system capable of mirror-image genetic replication and transcription

Wang, Zimou, Xu, Weiliang, Liu, Lei, Zhu, Ting F.·2016·Nature Chemistry

Abstract

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.

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Crossref · 10.1038/nchem.2517

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  • The synthesized and natural DNA polymerase systems operate without any cross-inhibition when mixed together in the presence of a racemic mixture of the constituents required for the reaction.

    “It was also demonstrated that the synthesized and natural DNA polymerase systems operate without any cross-inhibition when mixed together in the presence of a racemic mixture of the constituents required for the reaction”
  • A synthesized 174-residue (R)-polypeptide catalyzes the template-directed polymerization of L-DNA and its transcription into L-RNA.

    “Liu, Zhu and co-workers showed that a synthesized 174-residue (R)-polypeptide catalyzes the template-directed polymerization of L-DNA and its transcription into L-RNA.”
  • L-Polynucleotides and (R)-polypeptides were synthesized; and they exhibited chiral substrate specificity and biochemical properties that mirrored those of their natural counterparts.

    “L-Polynucleotides and (R)-polypeptides were synthesized; and expectedly they exhibited chiral substrate specificity and biochemical properties that mirrored those of their natural counterparts.”

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Authors
Wang, Z., Xu, W., Liu, L., & Zhu, T. F.
Affiliations
  • Ministry of Education of the People's Republic of China (CN)
  • Center for Life Sciences (CN)
Corresponding author
  • Liu, Lei
  • Zhu, Ting F.
Venue
Nature Chemistry
Published
2016-05-16
Volume
8
Issue
7
Pages
698-704
ISSN
  • 1755-4330 (ISSN-L)
  • 1755-4349
OpenAlex
W2395256178
Cited by
209
References
3
Citations by year
2026: 11 · 2025: 16 · 2024: 23 · 2023: 14 · 2022: 12 · 2021: 17 · 2020: 20 · 2019: 37 · 2018: 37 · 2017: 17 · 2016: 4
FWCI
15.14
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
Francis Crick Institute
Topics
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
homochirality, central dogma, template polymerization, chirality
MeSH terms
Amino Acids, DNA, DNA Replication, Nucleic Acid Conformation, RNA, Stereoisomerism, Transcription, Genetic, Polymerization

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