Bacterium with largest artificial genome

Researchers create a designer microbe with four million base pairs of great genetic material

The researchers' E. coli bacteria have a computer generated genome. © Christop Burgstedt / istock
Read out

Artificial life form: Researchers have equipped E. coli bacteria with a new, artificial genome. The synthetic genome consists of four million base pairs and differs from the natural model in more than 18, 000 positions. Thus, the newly created microbes have the largest artificial genome ever used to a living being.

The creation of artificial, tailor-made life forms is a dream of many genetic engineers. Several advances in synthetic biology have shown in recent years that scientists are getting closer to such "designer organisms".

Four million base pairs

Back in 2010, genetic engineering pioneer Craig Venter succeeded in synthetically reproducing the genetic material of a bacterium and planting living microbes. Since then researchers have, among other things, constructed synthetic chromosomes of yeast cells and even designed building instructions for completely new types of artificial bacteria on the computer.

Another success has now come from Julius Fredens of the Medical Research Council Laboratory of Molecular Biology at Cambridge and his colleagues: They have used a synthetic four million base pair genome for Escherichia coli bacteria - never before has a living being with such a large genetic make-up been created,

Design on the computer

The building instructions for their bacteria were first created by the scientists on the computer. Her idea: they not only wanted to copy the natural model, but also to create space for new information in their genetic material. They succeeded in doing so by removing naturally occurring redundancies from the gut microbiota genome. display

For example, natural cells use 64 different triple codes from the DNA bases adenine, cytosine, guanine and thymine. These so-called codons serve as construction instructions for the amino acids from which all protein molecules are assembled. There are, however, doublings: For example, there are six codons, all of which code for the amino acid serine.

61 instead of 64 codons

Fredens and his colleagues have now reduced the number of triples in their replica: their E. coli Syn61 baptized organism uses only 61 instead of 64 codons to produce all the necessary amino acids. The other three combinations are available as building instructions for new, artificial amino acids substances that are not found in nature.

The researchers then rebuilt the genetic material modified in this way in the laboratory and then, using the gene scissors CRISPR, subsequently infused it into pieces of normal E. coli cells. In fact, it turned out that these microbes were able to survive on a fully synthetic genome. Their genome differs in more than 18, 000 positions from its natural counterpart, as the team reports.

"New Records"

"With the synthesis of a four million base pair genome and the reduction of the genetic code to 61 codons, the scientists are setting new records in the field of synthetic genetics, " explain Benjamin Blount and Tom Ellis in a commentary in the journal Nature.

However, it is questionable how long these records will last. After all, researchers are already working on synthetically producing the twelve million base pair genome of brewer's yeast Saccharomyces cerevisiae, and an E. coli genome with only 57 codons is also planned.

Controversial technology

Such work means great potential. For the genome of computer-designed genomes can produce microbes that fulfill very specific purposes and produce, for example, vaccines, drugs and completely new biomolecules. At the same time, however, the creation of artificial life forms a significant interference with nature and evolution and is therefore highly controversial ethically. (Nature, 2019; doi: 10.1038 / s41586-019-1192-5)

Source: Nature Press

- Daniel Albat