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 demonstrated that two processes in the central dogma of molecular biology, the replication of DNA and transcription from DNA into RNA, can be catalyzed by a chemically synthesized D-polymerase on an L-DNA template. Using designed mutants of the D-polymerases, we also realized mirror-image PCR, gene transcription, reverse transcription, as well as mirror-image DNA and RNA sequencing. Next, toward building a mirror-image ribosome, we enzymatically transcribed the full-length mirror-image 5S ribosomal RNA, which can assemble with synthetic mirror-image ribosomal proteins into stable ribonucleoprotein complexes. Furthermore, we realized protein translation without aminoacyl-tRNA synthetases and ribozyme-catalyzed mirror-image tRNA charging. Our work is a small step toward realizing the mirror-image central dogma, and ultimately, the creation of mirror-image life. It also highlights the potential to exploit mirror-image biomolecules as a new class of research and therapeutic tools.

Interested students at Tsinghua University and postdoctoral candidates are welcome to contact Prof. Ting Zhu directly.