Xenobiology: a new form of life as the ultimate biosafety tool

Abstract

Synthetic biologists try to engineer useful biological systems that do not exist in nature. One of their goals is to design an orthogonal chromosome different from DNA and RNA, termed XNA for xeno nucleic acids. XNA exhibits a variety of structural chemical changes relative to its natural counterparts. These changes make this novel information-storing biopolymer "invisible" to natural biological systems. The lack of cognition to the natural world, however, is seen as an opportunity to implement a genetic firewall that impedes exchange of genetic information with the natural world, which means it could be the ultimate biosafety tool. Here I discuss, why it is necessary to go ahead designing xenobiological systems like XNA and its XNA binding proteins; what the biosafety specifications should look like for this genetic enclave; which steps should be carried out to boot up the first XNA life form; and what it means for the society at large.

Figure 1

The shared interest in Xenobiology is what the origin of life community, astrobiologists, system chemists, and synthetic biologists have in common.

Figure 2

Several xeno nucleotides can form Watson-Crick type double helices. These XNAs can be used as alternative information storing biopolymers. GNA, glycol nucleic acid; TNA, threose nucleic acid; HNA, hexitol nucleic acid (Illustrations by Simone Fuchs).

Figure 3

After 4 billion years, a new tree will sprout in the “Garden of Eden”. Non-DNA-based biological systems will be a safer place to conduct SB experiments and applications ( modified).

Figure 4

A small step for a molecule, but a big step for safety. The DNA world and the XNA world would be able to interact on the level of whole organisms (e.g., providing nutrients, capturing CO₂, detecting environmental pollutants) but would not able to exchange genetic material through horizontal gene transfer or via sexual reproduction. Therefore, it acts as a genetic firewall, but not as a biological firewall. In contrast to the natural world, the XNA world is completely dependent on external supply of essential biochemical building blocks that cannot be synthesized either by XNA or DNA organisms. Any “escape” of a xeno-organism out of the direct control of humans would automatically lead to death.

Figure 5

Transition from natural biological architecture to a synthetic architecture is achieved by gradually replacing natural elements with synthetic ones. A: Simplified schematic view on the natural replication, transcription and translation system. B: In the beginning an XNA biopolymer is a “useless” molecule that lacks cognition in the cell. C: XNA-dependent XNA polymerase allow first replication cycles. D: Subsequent XNA-dependent RNA polymerase allows the information in the XNA to be transcribed. E: Installing this system in a natural cell, both DNA and XNA provide RNA. F: Eliminating the DNA from the host cell; the XNA takes over the cell machinery. G: Another possible pathway uses XNA-dependent X2NA polymerase, where X2NA means a second type of XNA that is different from the first one (e.g., when XNA is HNA, X2NA could be TNA). H: To translate X2NA, it will be necessary to modify the ribosome, producing a xenosome (XS) responsible for protein assembly. * Proteins could also be assembled using unnatural amino acids, further enhancing the artificialness of the system. Other applications such as xeno-aptazymes (allosteric xenozymes) are also possible.