The overwhelmingly homochiral nature of life has left a puzzle as to whether mirror-image biology systems based on a chirally inverted version of molecular machinery could also exist. We initially developed a proof-of-concept mirror-image genetic replication and transcription system based on a synthetic 174-aa mirror-image African swine fever virus polymerase X (ASFV pol X) (Wang et al., 2016), followed by a more efficient and thermostable 352-aa mirror-image Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) that led to the realization of mirror-image PCR (Xu et al., 2017; Jiang et al., 2017), gene transcription, reverse transcription, as well as mirror-image DNA and RNA sequencing (Liu and Zhu, 2018; Wang et al., 2019). Toward building a mirror-image ribosome, we realized the assembly of mirror-image 5S ribonucleoprotein complexes (Ling et al., 2020), protein translation without aminoacyl-tRNA synthetases, and ribozyme-catalyzed mirror-image tRNA charging (Chen et al., 2021). More recently, we chemically synthesized a 90-kDa high-fidelity mirror-image Pfu DNA polymerase, enabling the accurate assembly of a kilobase-sized mirror-image gene and biostable storage of an entire paragraph of digital text in mirror-image DNA (Fan et al., 2021). Our work is a small step toward establishing the mirror-image central dogma of molecular biology. It also highlights the potential to exploit mirror-image biomolecules as a unique class of therapeutic and informational tools.
- Wang Z, Xu W, Liu L, Zhu TF. A synthetic molecular system capable of mirror-image genetic replication and transcription. Nature Chemistry, 8(7):698-704, (2016). [PDF]
- Xu W, Jiang W, Wang J, Yu L, Chen J, Liu X, Liu L, Zhu TF. Total chemical synthesis of a thermostable enzyme capable of polymerase chain reaction. Cell Discovery, 3:17008, (2017). [PDF]
- Jiang W, Zhang B, Fan C, Wang M, Wang J, Deng Q, Liu X, Chen J, Zheng J, Liu L, Zhu TF. Mirror-image polymerase chain reaction. Cell Discovery, 3:17037, (2017). [PDF]
- Liu X, Zhu TF. Sequencing mirror-image DNA chemically. Cell Chemical Biology, 25:1151-1156, (2018). [PDF]
- Wang M, Jiang W, Liu X, Wang J, Zhang B, Fan C, Liu L, Pena-Alcantara G, Ling JJ, Chen J, Zhu TF. Mirror-image gene transcription and reverse transcription. Chem, 5:848-857, (2019). [PDF]
- Ling JJ, Fan C, Qin H, Wang M, Chen J, Wittung-Stafshede P, Zhu TF. Mirror-image 5S ribonucleoprotein complexes. Angewandte Chemie International Edition, 59:3724-3731, (2020). [PDF]
- Chen J, Chen M, Zhu TF. Translating protein enzymes without aminoacyl-tRNA synthetases. Chem, 7:786-798, (2021). [PDF]
- Fan C, Deng Q, Zhu TF. Bioorthogonal information storage in L-DNA with a high-fidelity mirror-image Pfu DNA polymerase. Nature Biotechnology, Doi: 10.1038/s41587-021-00969-6 (2021). [PDF]
Interested students at Tsinghua University and postdoctoral candidates are welcome to contact Prof. Ting Zhu directly.