ᗺIO MIЯЯOЯ WOЯ⅃ᗡ

I, for one, welcome our new mirror image overlords

The world, at a molecular level, has a pretty specific orientation. Many molecules can be found with different isomers - they have the same molecular formula, the same sequence of bonds between those atoms, but their orientation in 3-D space differs. Importantly, DNA in nature has a specific orientation or chirality: we call it D-DNA, which forms a right handed helix, made up of specifically oriented deoxyribose.

The mirror image of D-DNA (using enantiomers of this sugar, L-deoxyribose) is called L-DNA, and forms a stable “left handed” helix.

Previously, L-DNA had been chemically synthesized in small quantities in labs… until now.

A paper that came out yesterday in Nature presents the chemical synthesis of a mirror image DNA polymerase. DNA polymerase is the enzyme that assembles a strand of DNA from nucleotides. These scientists assembled this mirror image polymerase amino acid by amino acid (almost 800 of them). This is truly a feat of protein engineering. Then, using this mirror polymerase, they produced kilobase length L-DNA. If we can make mirror polymerases then we can make way more L-DNA, much more easily, and that’s what they do.

But why is L-DNA or any mirror image biology relevant?

This is step 2 on a path of many steps to making mirror image life. We haven’t even synthesized a truly viable synthetic cell in the “natural” orientation, so we’re quite far away from building it mirrored. But, it’s an important step nonetheless: scientists use polymerases everyday to synthesize DNA.

L-DNA isn’t found in nature, which means it doesn’t get degraded in the ways that D-DNA does. This makes it useful for applications like information storage or tagging: in the Nature paper, the authors show that L-DNA in pond water is amplifiable and sequenceable for 1 year, whereas D-DNA under the same conditions could not be amplified after 1 day.

But information storage is just the tip of the iceberg.

  • We could make biological material that is resistant to degradation by natural biology: bacterial, viral, or pest resistance. Long lasting textiles, immortal yeast cells for bioproduction, or what about mirror-wood that never breaks down?

  • Tagging or barcoding with L-DNA - the presence of a short L-DNA sequence would identify something super quickly. Of course we have to get good at sequencing L-DNA, but you wouldn’t have to wade through billions of bases of D-DNA to get there.

  • Mirror enzymes to catalyze isomeric reactions - lots of interesting molecules come in very specific orientations. Mirror enzymes could catalyze reactions to produce drugs of only one stereoisomer, or specifically catalyze one isomer in a mixture.

  • Likewise, mirror ribosomes to produce mirror proteins open up a whole new class of active molecules for applications in therapy, diagnostics, materials, agriculture, you name it. Make mirror scents or mirror tastes, since our scent receptors can recognize different isomers.

Of course, we need to build a suite of tools to control these materials. Interestingly the authors are next going to build a L-DNase, an enzyme to break down L-DNA… because otherwise they can’t get rid of the damn stuff.

It’s unclear how this research will play out and we are likely many years from practical application, but the possibilities for mirror biology are pretty much endless.