World’s First Artificial Bacterial Genome Designed By A Computer Algorithm

On April 1st, 2019, Swiss scientists at ETH Zurich have been successful in creating the world’s first artificial(synthetic) bacterial genome created using just a computer. The synthetic biology researchers are the first to construct a simplified artificial bacterial genome with the help of computer algorithms. The new method greatly simplifies the production of large DNA molecules containing many hundreds of genes. With this method, they have built the first genome of a bacterium entirely designed by a computer algorithm. This would lead to better-engineered microorganisms for the production of therapeutics and other chemicals.

In a study published in PNAS, the researchers made C. ethensis-2.0 by cutting the C. ethensis genome down from its 4,000 genes to less than 680 — the ones identified as vital for a functional cell. The group then used computer algorithms to edit the building blocks of DNA in the remaining genes, in order to remove genetic complexity whilst preserving the core function of the genes. To check that the simplified code still works as intended, the researchers engineered bacteria to express isolated genes from C. ethensis-2.0, and aim to have the full genome in a living cell once it’s fully functional.

C. ethensis-2.0 (Caulobacter ethensis) is based on the genome of a well-studied and harmless freshwater bacterium, Caulobacter crescentus, which is a naturally occurring bacterium found in spring water, rivers and lakes around the globe. It does not cause any diseases. C. crescentus is also a model organism commonly used in research laboratories to study the life of bacteria.

As per Matthias Cristen,

“Currently, only 580 of the 680 genes are functional in our artificial genome. However, the method demonstrated by our research suggests that in the near future, the production of viable cells with artificial genome segments and whole genomes will be possible. We are currently working towards Caulobacter ethensis 3.0, a fully functional genome version.”

A Promising Technology With Advanced Applications

The method looks highly promising and has the potential to revolutionize the entire biotechnology industry. As, simplifying the bacterial genome makes it highly useful and easier to synthesize the genome (which is a technically challenging process) and to study the minimal genes needed for a cell to live. This could one day let scientists design simplified micro-organisms that are more efficient at producing DNA-based therapeutics and manufacturing enzymes and nutrients.

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It is a technically challenging process to manufacture long molecules of DNA, such as a genome. As a result, Venter’s group took ten years to synthesize the full bacterial genome. However, the Swiss group’s modern technology took a tenth of the time with minimal manufacturing costs. This highlights that synthetic biology is progressing fast, with synthetic genomes likely becoming a core part of the field in the coming years.

One of the leaders of the researcher’s group, Matthias Christen says,

“The time for this work was ripe. Worldwide, between 20 to 50 research groups are working to build such artificial bacteria. We were fortunate that in this case, we were the first to show the simplification of the chemical synthesis of whole bacterial genomes.”

In 2008, a  group of US researchers along with biologist John Craig Venter had made headlines for synthesizing the genome of the bacterial species ‘Mycoplasma Genitalium’ from scratch. Like Venter’s group, the Swiss group synthesized the genome of a bacterium, Caulobacter ethensis, a benign species that lives in freshwater. Unlike Venter’s group, however, they simplified the genome down to a bare-bones version, called C. ethensis-2.0.