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.
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.
Nat Chem. 2016 Jul;8(7):698-704. doi: 10.1038/nchem.2517. Epub 2016 May 16.
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.
生命在绝大多数情况下都是手性的,这给我们留下了一个谜题,即基于分子机制的手性反转版本的镜像生物系统是否也能存在。在这里,我们报告说,分子生物学中心法则的两个关键步骤,即 DNA 的模板指导聚合和 RNA 的转录,可以在 L-DNA 模板上由化学合成的 D-氨基酸聚合酶催化。我们还表明,两种手性镜像的非洲猪瘟病毒聚合酶 X 可以在无手性交叉抑制的情况下在外消旋混合物中运作,彼此之间的活性不受显著影响。此外,我们证明可以使用 D-氨基酸聚合酶酶促产生具有功能活性的 L-DNA 酶。建立这样具有相反手性的分子系统突出了利用酶促产生的镜像生物分子作为研究和治疗工具的潜力。