Large Artificial Genomes Generated

Scientists at the Max Planck Institute of Biochemistry have generated a system that is able to regenerate parts of its own DNA and protein building blocks. According to the team, this is the first time a “bottom-up” approach (the generation of life mimicking systems from inanimate building blocks) has been used to synthesize such a system.

Specifically, the researchers have optimized an in vitro expression system that synthesizes proteins based on a DNA blueprint. As a result of several improvements, the in vitro expression system is now able to synthesize DNA polymerases very efficiently. These DNA polymerases then replicate the DNA using nucleotides. According to Kai Libicher, first author of the study, which was published last week in Nature Communications, "Unlike previous studies, our system is able to read and copy comparatively long DNA genomes.

The scientists assembled the artificial genomes from up to eleven ring-shaped pieces of DNA. This modular structure enables them to insert or remove certain DNA segments easily. The largest modular genome reproduced by the researchers in the study consists of more than 116,000 base pairs, reaching the genome length of very simply cells.

Apart from encoding polymerases that are important for DNA replication, the artificial genome contains blueprints for further proteins, such as 30 translation factors originating from Escherischia coli.

In order to show that the new in vitro expression system is not only able to reproduce DNA, but is also able to produce its own translation factors, the researchers used mass spectrometry. With this analytic method, they determined the amount of proteins produced by the system. Surprisingly, some of the translation factors were even present in larger quantities after the reaction than added before. According to the researchers, this is an important step toward a continuously self-replicating system that mimics biological processes.

In the future, the scientists want to extend the artificial genome with additional DNA segments. In cooperation with colleagues from the research network MaxSynBio, they want to produce an enveloped system that is able to remain viable by adding nutrients and disposing of waste products. Such a minimal cell could then be used, for example, in biotechnology as a tailor-made production machine for natural substances or as a platform for building even more complex life-like systems.