What is a Semi-synthetic Organism?

By Reginald DaveyReviewed by Dr. Mary Cooke, Ph.D.

As a society, we face various issues in the modern world. Synthetic biology is an emerging field that is attempting to address these problems at the genetic level, and researchers in this field are pushing the boundaries of which proteins and processes can be developed and utilized.

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One of the latest pieces of research to be undertaken is the invention of semi-synthetic organisms. But what is a semi-synthetic organism?

Semi-synthetic organisms

A semi-synthetic organism is a genetically modified organism (usually a bacterium such as E. Coli), which has had unnatural genetic information inserted into its genome.

DNA is a complex molecule that codes for everything in an organism. From the smallest proteins to the largest organs and even some behavioral traits, all parts and details of an organism are built with the information provided by the genetic information.

DNA (deoxyribonucleic acid) is made up of nucleotides (which are themselves made of nucleosides that are linked to phosphate groups.) There are four naturally occurring nucleotides, which are: Adenine, Guanine, Cytosine, and Thymine. These base pairs are complementary, being of specific shapes that fit each other like hand and glove. RNA contains a fifth nucleotide which is specific to it, Uracil (U.) Uracil is replaced by Thymine in DNA.

Nucleotides fit together in base pairs in the following configuration only:

• Adenine-Thymine
• Cytosine-Guanine

Even though only these two base pairings can exist in nature, the combinations when scaled up to an entire genome lead to a wealth of information being encoded. So, it stands to reason that more base pairs equal more information.

Enter: The semi-synthetic organism.

A semi-synthetic organism is one that has been genetically modified to include artificial DNA base pairs. A new development in the fields of genetic engineering and synthetic biology, it opens the possibility of creating new proteins, drugs, and biofuels, amongst other useful substances, that do not exist in nature.

Synthetic biology: Developing the new frontier.

Research carried out by a team led by Yorke Zhang of the department of chemistry at the Scripp Institute in California, published in Nature in 2017, created a stable synthetic organism for the first time with two extra nucleotides – X and Y.

Building on research in 2014, in which members of the same team incorporated a synthetic base pair into a modified form of E. Coli, they proved that such an organism could exist and be viable for future development.

However, the stability issue was a major stumbling block for the team, as the semi-synthetic organism could not maintain the artificial nucleotides indefinitely during cell division. Making use of a refined engineering system made possible by the application of CRISPR-Cas9, an optimized Y molecule, and a new nucleotide transporter as a workaround, they managed to solve this problem.

The semi-synthetic organism was able to transcribe and translate the unnatural X and Y nucleotides to the same degree of efficiency as the naturally occurring A, C, G, and T nucleotides. Via a new transcription process, proteins containing ncAAs (non-canonical amino acids) were able to be synthesized.

The newly created organism represents the first stage in the development of this new and exciting technology. Whereas the organism was created with two artificial nucleotides, the team suggested that future semi-synthetic organisms could utilize further artificial base pairs (UBPs), which increases the possibilities for new biological processes being developed exponentially.

Semi-synthetic organisms: The future of biotechnology?

The field of synthetic biology is a cutting-edge development in life sciences that has been given attention by research teams over the last decade. With the advent of synthetic nucleotides which can pair with each other and other naturally occurring nucleotide base pairs, the possibilities for industries including drug development, environmental engineering, and genetic engineering are seemingly endless.

The arrival of semi-synthetic organisms may be a game-changer for these industries as we address the issues of modern society, such as climate change and antibiotic resistance.