Now, the Zhu lab has chemically synthesized a mirror-image of an enzyme called Pfu DNA polymerase, which is commonly used for PCR reactions. This enzyme is heat-resistant and has very high fidelity. But it’s also about twice as big as the polymerases the researchers had made before; the scientists had to synthesize it in two pieces and then link them together.
The researchers used the enzyme to copy a mirror-image gene that is 1,500 bases long, about 10 times as long as the earlier polymerases could manage. The gene the researchers chose encodes ribosomal RNA, so when they can transcribe it, they will have one part of a mirror-image ribosome. Once they get all the parts, they won’t have to rely on bulky synthetic methods to make mirror-image D-proteins anymore.
Long-lived
One potential use of mirror-image L-DNA is that, like its natural counterpart D-DNA, it can be used as a compact and reliable means of information storage. But unlike its natural counterpart, it can’t be degraded by enzymes, because no one has made mirror-image D-DNases that can degrade them yet. To demonstrate one application, Zhu made DNA barcodes for environmental water samples—you can think of the bar codes as using the sequence of bases to indicate things like “lotus pond, Beijing.” When he tried to amplify the normal, D-DNA barcode from a pond sample a day after adding it, it could not be found; it had been degraded. The mirror-image L-DNA barcode was still detectable a year later.
As if that weren’t clever enough, he and his lab ventured into steganography. They made a key molecule of DNA that is half-D and half-L; half-normal and half-mirror image. As a reference text, they encoded Pasteur’s 1860 paragraph speculating about mirror life into D-DNA. If the key is read with a normal DNA polymerase, it gives an error message when decoded using the Pasteur text. But if it is read with an L-DNA polymerase, it gives the secret message from the mirror DNA.
Obviously, Zhu’s team now intends to make mirror-image ribosomes to translate mirror-image mRNAs into mirror-image proteins. This is no small feat—ribosomes are very complex, involving dozens of proteins and several RNA molecules—but still, the researchers have gotten pretty far pretty fast. And of course, they also plan to make mirror-image D-DNases to “eliminate the information-storing L-DNA molecules after use as a biocontainment strategy.”
Nature Biotechnology, 2021 DOI: 10.1038/s41587-021-00969-6